Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
International Journal of Oncology
Join Editorial Board Propose a Special Issue
Print ISSN: 1019-6439 Online ISSN: 1791-2423
Journal Cover
December-2025 Volume 67 Issue 6

Full Size Image

Cover Legend PDF

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
December-2025 Volume 67 Issue 6

Full Size Image

Cover Legend PDF

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML

  • Supplementary Files
    • Supplementary_Data.pdf
Article Open Access

Adipocyte‑derived extracellular vesicles sustain mitochondrial metabolism in breast cancer cells: New insights into the cross‑talk between cancer cells and the tumor microenvironment

  • Authors:
    • Luca Gelsomino
    • Piercarlo Del Console
    • Maria Stella Murfuni
    • Marco Gaspari
    • Francesca Giordano
    • Giuseppina Daniela Naimo
    • Marco Fiorillo
    • Grazia Arpino
    • Mario Giuliano
    • Salvatore Panza
    • Daniela Bonofiglio
    • Sebastiano Andò
    • Ines Barone
    • Cinzia Giordano
    • Stefania Catalano
  • View Affiliations / Copyright

    Affiliations: Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Arcavacata di Rende (CS), I‑87036 Cosenza, Italy, Research Centre for Advanced Biochemistry and Molecular Biology, Department of Experimental and Clinical Medicine, Magna Graecia University of Catanzaro, I‑88100 Catanzaro, Italy, Department of Clinical Medicine and Surgery, University of Naples Federico II, I‑80131 Naples, Italy, Department of Experimental and Clinical Medicine, ‘Magna Graecia’, University of Catanzaro, I‑88100 Catanzaro, Italy
    Copyright: © Gelsomino et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 4.0].
  • Article Number: 100
    |
    Published online on: October 6, 2025
       https://doi.org/10.3892/ijo.2025.5806
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Adipocytes represent the most prominent component of breast tissue stroma and are recognized as significant contributors to the observed association between obesity and breast cancer (BC). It has been widely reported that dysfunctional adipose tissue in obesity has a profound effect on the biology of BC via the secretion of several bioactive molecules. Recently, extracellular vesicles (EVs), a heterogeneous group of membrane‑enclosed structures, have been recognized as key players in adipocyte‑BC cell communication. We previously demonstrated that adipocyte‑derived EVs promoted BC proliferation, migration, invasion, stemness and traits of epithelial‑to‑mesenchymal transition through the activation of hypoxia inducible factor‑1α (HIF‑1α). The present study, to further understand the impact of EVs in breast adiponcosis, investigated the effects of adipocyte‑derived EVs on the BC proteome. By employing liquid chromatography‑tandem mass spectrometry and different bioinformatic tools (such as Proteomap, STRING, FunRich, Reactome and MsigDB), it was found that adipocyte‑derived EVs regulated the expression of multiple proteins implicated in metabolic processes. Adipocyte‑derived EVs shifted cell metabolism towards oxidative phosphorylation in estrogen receptor‑positive (ER+) BC cell lines, including MCF‑7, ZR‑75‑1 and BT‑474 BC cells, through an increased mitochondrial activity along with an enhanced ATP production. These findings were extended by treating BC cells with EVs isolated from the serum of patients with BC classified as normal weight (NW‑EVs) and overweight or obese (OW/Ob‑EVs). Treatment of BC cells with OW/Ob‑EVs resulted in a significant increase of mitochondrial activity and ATP production compared with NW‑EVs. Of note, inhibition of HIF‑1α expression/activity reversed the effects of both adipocyte‑derived EVs and OW/Ob‑EVs on BC cell metabolism. In conclusion, the present study underscored the pivotal role of EVs in the BC‑obesity link, highlighting their involvement in driving metabolic reprogramming in ER+ BC cells through HIF‑1α.
View Figures

Figure 1

Schematic representation of the
complete workflow to analyze changes in the proteome profile of
MCF-7 BC cells treated with or without EVs-derived from 3T3-L1A (2
μg/ml) for 48 h. The figure was created using BioRender
(https://biorender.com). EVs, extracellular
vesicles; 3T3-L1A, murine 3T3-L1 adipocytes; MCF-7, estrogen
receptor-positive breast cancer cells; FASP, filter-aided sample
protocol; SCX, strong cation exchange; LC-MS/MS; liquid
chromatography-tandem mass spectrometry; DIA, data independent
acquisition.

Figure 2

Proteomic analysis of MCF-7 BC cells
treated with EVs isolated from mature 3T3-L1 adipocytes. (A) The
PCA plot shows the control group (red spheres) and
3T3-L1A-EV-treated group (blue spheres) using R package (version
4.4.2). (B) Volcano plot displaying all identified proteins from
MCF-7 BC cells treated with 3T3-L1A-EVs (red dots for upregulated
proteins; blue dots for downregulated proteins). (C) Heatmap
illustrating the differentially expressed proteins in control and
EV-treated MCF-7 cells identified by LC-MS/MS. The color scale
shows the relative amount of each protein across the six samples,
with red indicating upregulation and green indicating
downregulation; black represents the median expression level. (D)
Proteins identified in MCF-7 BC cells treated with 3T3-L1A-EVs were
subjected to a Venn diagram for comparison with proteins reported
in the Vesiclepedia and Exocarta databases. (E) Proteins identified
in MCF-7 BC cells treated with 3T3-L1A-EVs were subjected to a Venn
diagram for comparison with proteins reported in the 'extracellular
exosome' gene ontology (GO:0070062). EVs, extracellular vesicles;
PCA, principal component analysis; MCF-7, estrogen
receptor-positive breast cancer cells; 3T3-L1A, murine 3T3-L1
adipocytes.

Figure 3

Functional enrichment analysis of the
identified de-regulated proteins. (A) By using Proteomaps different
levels of information are shown and each polygon represents a
single Kyoto Encyclopedia of Genes and Genomes pathway clustered in
five categories with different colors: Environmental information
processing (cyan), genetic information processing (blue),
metabolism (orange), cellular processes (red) and organismal
systems (pink). The larger areas have more assigned proteins. (B)
Interaction network derived from STRING database. Only proteins
with an interaction are shown, as the confidence of the interaction
was set to medium (0.4) and gave total 98 nodes; 70 edges with an
average node degree of 1.44 and PPI (protein-protein interaction)
enrichment P-value of 0.00225. Graphical representation of STRING
Gene Ontology (GO) analysis of the GO terms (C) 'Biological
Process' and (D) 'Annotated Keyword'. Bubble plot showing the 20
most markedly enriched pathways in the (E) REACTOME pathways and
(F) MSigDB databases. BP, biological process; CC, cellular
compartment.

Figure 4

3T3L-1A-EVs support metabolism of
MCF-7 BC cells. The seahorse XF-e96 analyzer was used to assess the
mitochondrial and glycolytic metabolic activity of MCF-7 cells
untreated (-) or treated with 3T3-L1A-EVs (2 μg/ml) for 48
h. (A) OCR flux, histograms of different mitochondrial respiratory
parameters such as (B) basal and (C) maximal respiration are shown.
(D) ECAR flux and relative histograms of (E) glycolysis, (F)
glycolytic reserve and (G) glycolytic reserve capacity. Data were
analyzed using Student's t test and are represented as mean ± SEM
of five biological replicates from three independent experiments
and normalized to protein content (SRB assay). *P≤0.05;
**P≤0.01. 3T3-L1A, murine 3T3-L1 adipocytes; OCR, oxygen
consumption rates; ECAR, extracellular acidification rates; SRB,
sulforhodamine B; FCCP, carbonyl cyanide
p-trifluoromethoxyphenylhydrazone; Rot, rotenone; Ant, Antimycin
A.

Figure 5

3T3L-1A-EVs sustain mitochondrial
metabolism of ZR-75-1 and BT-474 BC cells. The seahorse XF-e96
analyzer was used to assess the mitochondrial metabolic profile of
ZR-75-1 and BT-474 cells untreated (-) or treated with 3T3-L1A-EVs
(2 μg/ml) for 48 h. (A and D) OCR flux, histograms of
different mitochondrial respiratory parameters such as (B and E)
basal and (C and F) maximal respiration are shown. Data were
analyzed using Student's t test and are represented as mean ± SEM
of five biological replicates from two independent experiments and
normalized to protein content (SRB assay). *P≤0.05. OCR,
oxygen consumption rate, SRB, sulforhodamine B; FCCP, carbonyl
cyanide p-trifluoromethoxyphenylhydrazone; Rot, rotenone; Ant,
Antimycin A.

Figure 6

3T3L-1A-EVs affect mitochondrial
function and ATP production in MCF-7 cells. (A) ATP production in
cells treated as indicated. Mitochondrial mass (B) and
mitochondrial membrane potential (C) along with relative dot plots
of gating strategy from FACS analysis. (D) Ratio between
mitochondrial membrane potential and mitochondrial mass. (E)
Mitochondrial marker expression (V-ATP5A, III-UQCRC2, II-SDHB,
IV-COXII and I-NDUFAB8) in MCF-7 BC cells untreated (-) or treated
with 3T3-L1A-EVs (2 μg/ml) for 48 h. The outer mitochondrial
membrane marker TOM20 and GAPDH were used as controls for equal
loading and transfer. The histograms represent the mean ± SD of
three separate experiments in which band intensities were evaluated
in terms of OD and expressed as fold induction over untreated
cells. Data were represented as mean ± SD of three biological
replicates from three independent experiments. *P≤0.05;
**P≤0.01. 3T3-L1A, murine 3T3-L1 adipocytes; EVs,
extracellular vesicles; OD, optical density arbitrary units; M,
mitotracker.

Figure 7

HIF-1α specific blockade inhibits
3T3L-1A-EV effects on cell metabolism and energy production. The
seahorse XF-e96 analyzer was used to assess the mitochondrial
metabolic profile of MCF-7 cells untreated (-) or treated with
3T3-L1A-EVs (2 μg/ml) for 48 h, in the presence or not of
HIF-1α specific inhibitor (KC7F2, 20 μM). (A) OCR flux and
histograms of different mitochondrial respiratory parameters (B)
basal and (C) maximal respiration. Data were analyzed using one-way
ANOVA with Tukey's multiple comparisons post hoc test and
represented as ± SEM of five biological replicates from three
independent experiments and normalized to protein content (SRB
assay). (D) ATP production; (E) ratio between mitochondrial
membrane potential and mitochondrial mass of MCF-7 cells untreated
(-) or treated with 3T3-L1A-EVs (2 μg/ml) for 48 h, in the
presence or not of HIF-1α specific inhibitor (KC7F2 20 μM).
Data were analyzed using one-way ANOVA with Tukey's multiple
comparisons post hoc test and represented as ± SD of three
biological replicates from three independent experiments.
*P≤0.05; **P≤0.01. 3T3-L1A, murine 3T3-L1
adipocytes; EVs, extracellular vesicles; OCR, oxygen consumption
rates; SRB, sulforhodamine B; FCCP, carbonyl cyanide
p-trifluoromethoxyphenylhydrazone; Rot, rotenone; Ant, Antimycin
A.

Figure 8

Silencing HIF-1α expression inhibits
3T3L-1A-EV effects on cell metabolism and energy production. (A)
Immunoblot analysis of HIF-1α in whole cell lysate of MCF-7 cells
transfected with negative control siRNA or siHIF-1α for 48 h.
β-Actin was used as a control of equal loading and transfer. The
seahorse XF-e96 analyzer was used to assess the mitochondrial
metabolic profile of MCF-7 cells untreated (-) or treated with
3T3-L1A-EVs (2 μg/ml) for 48 h, previously transfected for
48 h with either siRNA or with siHIF-1α. (B) OCR flux and
histograms of different mitochondrial respiratory parameters such
as (C) basal and (D) maximal respiration. Data were analyzed using
Student's t test and represented as ± SEM of five biological
replicates from two independent experiments and normalized to
protein content (SRB assay). (E) ATP production; (F) ratio between
mitochondrial membrane potential and mitochondrial mass of MCF-7
cells transfected for 48 h with either siRNA or with siHIF-1α and
then untreated (-) or treated with 3T3-L1A-EVs (2 μg/ml) for
48 h. Data were analyzed using Student's t test and represented as
± SD of three biological replicates from two independent
experiments. *P≤0.05; **P≤0.01. HIF-1α,
hypoxia inducible factor-1α; 3T3-L1A, murine 3T3-L1 adipocytes;
EVs, extracellular vesicles; si, small interfering; OCR, oxygen
consumption rates; SRB, sulforhodamine B; FCCP, carbonyl cyanide
p-trifluoromethoxyphenylhydrazone; Rot, rotenone; Ant, Antimycin
A.

Figure 9

EVs derived from overweight/obese
patients with BC enhance mitochondrial phosphorylation and ATP
production in BC cells through HIF-1α. The seahorse XF-e96 analyzer
was used to assess the mitochondrial metabolic profile of MCF-7
cells treated with EVs (2 μg/ml) isolated from the serum of
NW and OW/Ob patients with BC for 48 h, in the presence or not of
HIF-1α specific inhibitor (KC7F2; 20 μM). (A) OCR flux and
histograms of different mitochondrial respiratory parameters such
as (B) basal (C) and maximal respiration are shown. Data were
analyzed using one-way ANOVA with Tukey's multiple comparisons post
hoc test and represented as ± SEM of five biological replicates
from two independent experiments and normalized to protein content
(SRB assay). ATP production in MCF-7 cells treated as indicated (D)
or transfected with siHIF-1α (E). Data were analyzed using one-way
ANOVA with Tukey's multiple comparisons post hoc test and
represented as ± SD of three biological replicates from two
independent experiments. *P≤0.05; **P≤0.01.
EVs, extracellular vesicles; HIF-1α, hypoxia inducible factor-1α;
NW, normal weight; OW/Ob, overweight/obese; OCR, oxygen consumption
rates; SRB, sulforhodamine B; FCCP, carbonyl cyanide
p-trifluoromethoxyphenylhydrazone; Rot, rotenone; Ant, Antimycin
A.
View References

1 

Ambrosio MR, Adriaens M, Derks K, Migliaccio T, Costa V, Liguoro D, Cataldi S, D'Esposito V, Maneli G, Bassolino R, et al: Glucose impacts onto the reciprocal reprogramming between mammary adipocytes and cancer cells. Sci Rep. 14:246742024. View Article : Google Scholar : PubMed/NCBI

2 

Dominiak A, Chelstowska B, Olejarz W and Nowicka G: Communication in the cancer microenvironment as a target for therapeutic interventions. Cancers (Basel). 12:12322020. View Article : Google Scholar : PubMed/NCBI

3 

Zhou JX, Taramelli R, Pedrini E, Knijnenburg T and Huang S: Extracting intercellular signaling network of cancer tissues using ligand-receptor expression patterns from whole-tumor and single-cell transcriptomes. Sci Rep. 7:88152017. View Article : Google Scholar : PubMed/NCBI

4 

Andò S, Gelsomino L, Panza S, Giordano C, Bonofiglio D, Barone I and Catalano S: Obesity, leptin and breast cancer: epidemiological evidence and proposed mechanisms. Cancers (Basel). 11:622019. View Article : Google Scholar : PubMed/NCBI

5 

Gelsomino L, Giordano C, Camera GL, Sisci D, Marsico S, Campana A, Tarallo R, Rinaldi A, Fuqua S, Leggio A, et al: Leptin signaling contributes to aromatase inhibitor resistant breast cancer cell growth and activation of macrophages. Biomolecules. 10:5432020. View Article : Google Scholar : PubMed/NCBI

6 

Catalano S, Leggio A, Barone I, De Marco R, Gelsomino L, Campana A, Malivindi R, Panza S, Giordano C, Liguori A, et al: A novel leptin antagonist peptide inhibits breast cancer growth in vitro and in vivo. J Cell Mol Med. 19:1122–1132. 2015. View Article : Google Scholar : PubMed/NCBI

7 

Barone I, Catalano S, Gelsomino L, Marsico S, Giordano C, Panza S, Bonofiglio D, Bossi G, Covington KR, Fuqua SA and Andò S: Leptin mediates tumor-stromal interactions that promote the invasive growth of breast cancer cells. Cancer Res. 72:1416–1427. 2012. View Article : Google Scholar : PubMed/NCBI

8 

Giordano C, Vizza D, Panza S, Barone I, Bonofiglio D, Lanzino M, Sisci D, De Amicis F, Fuqua SA, Catalano S and Andò S: Leptin increases HER2 protein levels through a STAT3-mediated up-regulation of Hsp90 in breast cancer cells. Mol Oncol. 7:379–391. 2013. View Article : Google Scholar

9 

Devericks EN, Carson MS, McCullough LE, Coleman MF and Hursting SD: The obesity-breast cancer link: A multidisciplinary perspective. Cancer Metastasis Rev. 41:607–625. 2022. View Article : Google Scholar : PubMed/NCBI

10 

Andò S, Naimo GD, Gelsomino L, Catalano S and Mauro L: Novel insights into adiponectin action in breast cancer: Evidence of its mechanistic effects mediated by ERα expression. Obes Rev. 21:e130042020. View Article : Google Scholar

11 

Mauro L, Naimo GD, Gelsomino L, Malivindi R, Bruno L, Pellegrino M, Tarallo R, Memoli D, Weisz A, Panno ML and Andò S: Uncoupling effects of estrogen receptor α on LKB1/AMPK interaction upon adiponectin exposure in breast cancer. FASEB J. 32:4343–4355. 2018. View Article : Google Scholar : PubMed/NCBI

12 

Naimo GD, Forestiero M, Paoli A, Malivindi R, Gelsomino L, Győrffy B, Leonetti AE, Giordano F, Panza S, Conforti FL, et al: ERα/LKB1 complex upregulates E-cadherin expression and stimulates breast cancer growth and progression upon adiponectin exposure. Int J Cancer. 153:1257–1272. 2023. View Article : Google Scholar : PubMed/NCBI

13 

Naimo GD, Gelsomino L, Catalano S, Mauro L and Andò S: Interfering role of ERα on adiponectin action in breast cancer. Front Endocrinol (Lausanne). 11:662020. View Article : Google Scholar

14 

Hartwig S, De Filippo E, Göddeke S, Knebel B, Kotzka J, Al-Hasani H, Roden M, Lehr S and Sell H: Exosomal proteins constitute an essential part of the human adipose tissue secretome. Biochim Biophys Acta Proteins Proteom. 1867:1401722019. View Article : Google Scholar

15 

Durcin M, Fleury A, Taillebois E, Hilairet G, Krupova Z, Henry C, Truchet S, Trötzmüller M, Köfeler H, Mabilleau G, et al: Characterisation of adipocyte-derived extracellular vesicle subtypes identifies distinct protein and lipid signatures for large and small extracellular vesicles. J Extracell Vesicles. 6:13056772017. View Article : Google Scholar : PubMed/NCBI

16 

Wang J, Wu Y, Guo J, Fei X, Yu L and Ma S: Adipocyte-derived exosomes promote lung cancer metastasis by increasing MMP9 activity via transferring MMP3 to lung cancer cells. Oncotarget. 8:81880–81891. 2017. View Article : Google Scholar : PubMed/NCBI

17 

Fontana F, Anselmi M, Carollo E, Sartori P, Procacci P, Carter D and Limonta P: Adipocyte-derived extracellular vesicles promote prostate cancer cell aggressiveness by enabling multiple phenotypic and metabolic changes. Cells. 11:23882022. View Article : Google Scholar : PubMed/NCBI

18 

Lazar I, Clement E, Dauvillier S, Milhas D, Ducoux-Petit M, LeGonidec S, Moro C, Soldan V, Dalle S, Balor S, et al: Adipocyte exosomes promote melanoma aggressiveness through fatty acid oxidation: A novel mechanism linking obesity and cancer. Cancer Res. 76:4051–4057. 2016. View Article : Google Scholar : PubMed/NCBI

19 

Liu Y, Tan J, Ou S, Chen J and Chen L: Adipose-derived exosomes deliver miR-23a/b to regulate tumor growth in hepatocellular cancer by targeting the VHL/HIF axis. J Physiol Biochem. 75:391–401. 2019. View Article : Google Scholar : PubMed/NCBI

20 

La Camera G, Gelsomino L, Malivindi R, Barone I, Panza S, De Rose D, Giordano F, D'Esposito V, Formisano P, Bonofiglio D, et al: Adipocyte-derived extracellular vesicles promote breast cancer cell malignancy through HIF-1α activity. Cancer Lett. 521:155–168. 2021. View Article : Google Scholar : PubMed/NCBI

21 

Jafari N, Kolla M, Meshulam T, Shafran JS, Qiu Y, Casey AN, Pompa IR, Ennis CS, Mazzeo CS, Rabhi N, et al: Adipocyte-derived exosomes may promote breast cancer progression in type 2 diabetes. Sci Signal. 14:eabj28072021. View Article : Google Scholar : PubMed/NCBI

22 

Barone I, Gelsomino L, Accattatis FM, Giordano F, Gyorffy B, Panza S, Giuliano M, Veneziani BM, Arpino G, De Angelis C, et al: Analysis of circulating extracellular vesicle derived microRNAs in breast cancer patients with obesity: A potential role for Let-7a. J Transl Med. 21:2322023. View Article : Google Scholar : PubMed/NCBI

23 

Aliakbari F, Stocek NB, Cole-André M, Gomes J, Fanchini G, Pasternak SH, Christiansen G, Morshedi D, Volkening K and Strong MJ: A methodological primer of extracellular vesicles isolation and characterization via different techniques. Biol Methods Protoc. 9:bpae0092024. View Article : Google Scholar : PubMed/NCBI

24 

Wu JY, Li YJ, Hu XB, Huang S and Xiang DX: Preservation of small extracellular vesicles for functional analysis and therapeutic applications: A comparative evaluation of storage conditions. Drug Deliv. 28:162–170. 2021. View Article : Google Scholar : PubMed/NCBI

25 

Gelsomino L, Caruso A, Tasan E, Leonetti AE, Malivindi R, Naimo GD, Giordano F, Panza S, Gu G, Perrone B, et al: Evidence that CRISPR-Cas9 Y537S-mutant expressing breast cancer cells activate Yes-associated protein 1 to driving the conversion of normal fibroblasts into cancer-associated fibroblasts. Cell Commun Signal. 22:5452024. View Article : Google Scholar : PubMed/NCBI

26 

Murfuni MS, Prestagiacomo LE, Giuliano A, Gabriele C, Signoretti S, Cuda G and Gaspari M: Evaluation of PAC and FASP performance: DIA-Based quantitative proteomic Analysis. Int J Mol Sci. 25:51412024. View Article : Google Scholar : PubMed/NCBI

27 

Rappsilber J, Mann M and Ishihama Y: Protocol for micro-purification, enrichment, pre-fractionation and storage of peptides for proteomics using StageTips. Nat Protoc. 2:1896–1906. 2007. View Article : Google Scholar : PubMed/NCBI

28 

Tyanova S, Temu T, Sinitcyn P, Carlson A, Hein MY, Geiger T, Mann M and Cox J: The Perseus computational platform for comprehensive analysis of (prote)omics data. Nat Methods. 13:731–740. 2016. View Article : Google Scholar : PubMed/NCBI

29 

Liebermeister W, Noor E, Flamholz A, Davidi D, Bernhardt J and Milo R: Visual account of protein investment in cellular functions. Proc Natl Acad Sci USA. 111:8488–8493. 2014. View Article : Google Scholar : PubMed/NCBI

30 

Binder MJ and Pedley AM: The roles of molecular chaperones in regulating cell metabolism. FEBS Lett. 597:1681–1701. 2023. View Article : Google Scholar : PubMed/NCBI

31 

Caruso A, Gelsomino L, Panza S, Accattatis FM, Naimo GD, Barone I, Giordano C, Catalano S and Andò S: Leptin: A heavyweight player in obesity-related cancers. Biomolecules. 13:10842023. View Article : Google Scholar : PubMed/NCBI

32 

Gelsomino L, Naimo GD, Malivindi R, Augimeri G, Panza S, Giordano C, Barone I, Bonofiglio D, Mauro L, Catalano S and Andò S: Knockdown of leptin receptor affects macrophage phenotype in the tumor microenvironment inhibiting breast cancer growth and progression. Cancers (Basel). 12:20782020. View Article : Google Scholar : PubMed/NCBI

33 

Gelsomino L, Naimo GD, Catalano S, Mauro L and Andò S: The emerging role of adiponectin in female malignancies. Int J Mol Sci. 20:21272019. View Article : Google Scholar : PubMed/NCBI

34 

Elia I and Haigis MC: Metabolites and the tumour microenvironment: From cellular mechanisms to systemic metabolism. Nat Metab. 3:21–32. 2021. View Article : Google Scholar : PubMed/NCBI

35 

Chae HS and Hong ST: Overview of cancer metabolism and signaling transduction. Int J Mol Sci. 24:122022. View Article : Google Scholar

36 

Cantor JR and Sabatini DM: Cancer cell metabolism: One hallmark, many faces. Cancer Discov. 2:881–898. 2012. View Article : Google Scholar : PubMed/NCBI

37 

Warburg O: On the origin of cancer cells. Science. 123:309–314. 1956. View Article : Google Scholar : PubMed/NCBI

38 

Yang J, Shay C, Saba NF and Teng Y: Cancer metabolism and carcinogenesis. Exp Hematol Oncol. 13:102024. View Article : Google Scholar : PubMed/NCBI

39 

Pavlova NN, Zhu J and Thompson CB: The hallmarks of cancer metabolism: Still emerging. Cell Metab. 34:355–377. 2022. View Article : Google Scholar : PubMed/NCBI

40 

Pham DV and Park PH: Tumor metabolic reprogramming by adipokines as a critical driver of obesity-associated cancer progression. Int J Mol Sci. 22:14442021. View Article : Google Scholar : PubMed/NCBI

41 

Balaban S, Shearer RF, Lee LS, van Geldermalsen M, Schreuder M, Shtein HC, Cairns R, Thomas KC, Fazakerley DJ, Grewal T, et al: Adipocyte lipolysis links obesity to breast cancer growth: Adipocyte-derived fatty acids drive breast cancer cell proliferation and migration. Cancer Metab. 5:12017. View Article : Google Scholar : PubMed/NCBI

42 

Brown KA: Metabolic pathways in obesity-related breast cancer. Nat Rev Endocrinol. 17:350–363. 2021. View Article : Google Scholar : PubMed/NCBI

43 

Müller G, Schneider M, Biemer-Daub G and Wied S: Microvesicles released from rat adipocytes and harboring glycosylphosphatidylinositol-anchored proteins transfer RNA stimulating lipid synthesis. Cell Signal. 23:1207–1223. 2011. View Article : Google Scholar : PubMed/NCBI

44 

Clement E, Lazar I, Attané C, Carrié L, Dauvillier S, Ducoux-Petit M, Esteve D, Menneteau T, Moutahir M, Le Gonidec S, et al: Adipocyte extracellular vesicles carry enzymes and fatty acids that stimulate mitochondrial metabolism and remodeling in tumor cells. EMBO J. 39:e1025252020. View Article : Google Scholar : PubMed/NCBI

45 

Liu S, Benito-Martin A, Pelissier Vatter FA, Hanif SZ, Liu C, Bhardwaj P, Sethupathy P, Farghli AR, Piloco P, Paik P, et al: Breast adipose tissue-derived extracellular vesicles from obese women alter tumor cell metabolism. EMBO Rep. 24:e573392023. View Article : Google Scholar : PubMed/NCBI

46 

Zhang Q, Deng T, Zhang H, Zuo D, Zhu Q, Bai M, Liu R, Ning T, Zhang L, Yu Z, et al: Adipocyte-derived exosomal MTTP suppresses ferroptosis and promotes chemoresistance in colorectal cancer. Adv Sci (Weinh). 9:e22033572022. View Article : Google Scholar : PubMed/NCBI

47 

Galluzzi L, Kepp O, Vander Heiden MG and Kroemer G: Metabolic targets for cancer therapy. Nat Rev Drug Discov. 12:829–846. 2013. View Article : Google Scholar : PubMed/NCBI

48 

Martinez-Outschoorn UE, Peiris-Pagés M, Pestell RG, Sotgia F and Lisanti MP: Cancer metabolism: A therapeutic perspective. Nat Rev Clin Oncol. 14:11–31. 2017. View Article : Google Scholar

49 

Hanahan D and Weinberg RA: Hallmarks of cancer: The next generation. Cell. 144:646–674. 2011. View Article : Google Scholar : PubMed/NCBI

50 

Zhou C, Huang YQ, Da MX, Jin WL and Zhou FH: Adipocyte-derived extracellular vesicles: Bridging the communications between obesity and tumor microenvironment. Discov Oncol. 14:922023. View Article : Google Scholar : PubMed/NCBI

51 

Blandin A, Dugail I, Hilairet G, Ponnaiah M, Ghesquière V, Froger J, Ducheix S, Fizanne L, Boursier J, Cariou B, et al: Lipidomic analysis of adipose-derived extracellular vesicles reveals specific EV lipid sorting informative of the obesity metabolic state. Cell Rep. 42:1121692023. View Article : Google Scholar : PubMed/NCBI

52 

Gelsomino L, Barone I, Caruso A, Giordano F, Brindisi M, Morello G, Accattatis FM, Panza S, Cappello AR, Bonofiglio D, et al: Proteomic profiling of extracellular vesicles released by leptin-treated breast cancer cells: A potential role in cancer metabolism. Int J Mol Sci. 23:129412022. View Article : Google Scholar : PubMed/NCBI

53 

Sakaue T, Dorayappan KDP, Zingarelli R, Khadraoui W, Anbalagan M, Wallbillich J, Bognar B, Wanner R, Cosgrove C, Suarez A, et al: Obesity-induced extracellular vesicles proteins drive the endometrial cancer pathogenesis: Therapeutic potential of HO-3867 and Metformin. Oncogene. 43:3586–3597. 2024. View Article : Google Scholar : PubMed/NCBI

54 

Mathiesen A, Haynes B, Huyck R, Brown M and Dobrian A: Adipose tissue-derived extracellular vesicles contribute to phenotypic plasticity of prostate cancer cells. Int J Mol Sci. 24:12292023. View Article : Google Scholar : PubMed/NCBI

55 

Giordano C, Gelsomino L, Barone I, Panza S, Augimeri G, Bonofiglio D, Rovito D, Naimo GD, Leggio A, Catalano S and Andò S: Leptin modulates exosome biogenesis in breast cancer cells: An additional mechanism in cell-to-cell communication. J Clin Med. 8:10272019. View Article : Google Scholar : PubMed/NCBI

56 

Liu Q, Guan C, Liu C, Li H, Wu J and Sun C: Targeting hypoxia-inducible factor-1alpha: A new strategy for triple-negative breast cancer therapy. Biomed Pharmacother. 156:1138612022. View Article : Google Scholar : PubMed/NCBI

57 

Zhi S, Chen C, Huang H, Zhang Z, Zeng F and Zhang S: Hypoxia-inducible factor in breast cancer: Role and target for breast cancer treatment. Front Immunol. 15:13708002024. View Article : Google Scholar : PubMed/NCBI

58 

Luo S, Jiang Y, Zheng A, Zhao Y, Wu X, Li M, Du F, Chen Y, Deng S, Chen M, et al: Targeting hypoxia-inducible factors for breast cancer therapy: A narrative review. Front Pharmacol. 13:10646612022. View Article : Google Scholar : PubMed/NCBI

59 

Liu ZJ, Semenza GL and Zhang HF: Hypoxia-inducible factor 1 and breast cancer metastasis. J Zhejiang Univ Sci B. 16:32–43. 2015. View Article : Google Scholar : PubMed/NCBI

60 

Infantino V, Santarsiero A, Convertini P, Todisco S and Iacobazzi V: Cancer cell metabolism in hypoxia: Role of HIF-1 as Key regulator and therapeutic target. Int J Mol Sci. 22:57032021. View Article : Google Scholar : PubMed/NCBI

61 

Yun Z, Maecker HL, Johnson RS and Giaccia AJ: Inhibition of PPAR gamma 2 gene expression by the HIF-1-regulated gene DEC1/Stra13: A mechanism for regulation of adipogenesis by hypoxia. Dev Cell. 2:331–341. 2002. View Article : Google Scholar : PubMed/NCBI

62 

Yu X, Zhang T, Cheng X and Ma L: Breast cancer cells and adipocytes in hypoxia: Metabolism regulation. Discov Oncol. 15:112024. View Article : Google Scholar : PubMed/NCBI

63 

Aird R, Wills J, Roby KF, Bénézech C, Stimson RH, Wabitsch M, Pollard JW, Finch A and Michailidou Z: Hypoxia-driven metabolic reprogramming of adipocytes fuels cancer cell proliferation. Front Endocrinol (Lausanne). 13:9895232022. View Article : Google Scholar : PubMed/NCBI

64 

Mirabelli M, Misiti R, Sicilia L, Brunetti FS, Chiefari E, Brunetti A and Foti DP: Hypoxia in human obesity: New insights from inflammation towards insulin resistance-a narrative review. Int J Mol Sci. 25:98022024. View Article : Google Scholar : PubMed/NCBI

65 

Gaspar JM and Velloso LA: Hypoxia inducible factor as a central regulator of metabolism-implications for the development of obesity. Front Neurosci. 12:8132018. View Article : Google Scholar

66 

He Q, Gao Z, Yin J, Zhang J, Yun Z and Ye J: Regulation of HIF-1{alpha} activity in adipose tissue by obesity-associated factors: Adipogenesis, insulin, and hypoxia. Am J Physiol Endocrinol Metab. 300:E877–E885. 2011. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Gelsomino L, Del Console P, Murfuni MS, Gaspari M, Giordano F, Naimo GD, Fiorillo M, Arpino G, Giuliano M, Panza S, Panza S, et al: Adipocyte‑derived extracellular vesicles sustain mitochondrial metabolism in breast cancer cells: New insights into the cross‑talk between cancer cells and the tumor microenvironment. Int J Oncol 67: 100, 2025.
APA
Gelsomino, L., Del Console, P., Murfuni, M.S., Gaspari, M., Giordano, F., Naimo, G.D. ... Catalano, S. (2025). Adipocyte‑derived extracellular vesicles sustain mitochondrial metabolism in breast cancer cells: New insights into the cross‑talk between cancer cells and the tumor microenvironment. International Journal of Oncology, 67, 100. https://doi.org/10.3892/ijo.2025.5806
MLA
Gelsomino, L., Del Console, P., Murfuni, M. S., Gaspari, M., Giordano, F., Naimo, G. D., Fiorillo, M., Arpino, G., Giuliano, M., Panza, S., Bonofiglio, D., Andò, S., Barone, I., Giordano, C., Catalano, S."Adipocyte‑derived extracellular vesicles sustain mitochondrial metabolism in breast cancer cells: New insights into the cross‑talk between cancer cells and the tumor microenvironment". International Journal of Oncology 67.6 (2025): 100.
Chicago
Gelsomino, L., Del Console, P., Murfuni, M. S., Gaspari, M., Giordano, F., Naimo, G. D., Fiorillo, M., Arpino, G., Giuliano, M., Panza, S., Bonofiglio, D., Andò, S., Barone, I., Giordano, C., Catalano, S."Adipocyte‑derived extracellular vesicles sustain mitochondrial metabolism in breast cancer cells: New insights into the cross‑talk between cancer cells and the tumor microenvironment". International Journal of Oncology 67, no. 6 (2025): 100. https://doi.org/10.3892/ijo.2025.5806
Copy and paste a formatted citation
x
Spandidos Publications style
Gelsomino L, Del Console P, Murfuni MS, Gaspari M, Giordano F, Naimo GD, Fiorillo M, Arpino G, Giuliano M, Panza S, Panza S, et al: Adipocyte‑derived extracellular vesicles sustain mitochondrial metabolism in breast cancer cells: New insights into the cross‑talk between cancer cells and the tumor microenvironment. Int J Oncol 67: 100, 2025.
APA
Gelsomino, L., Del Console, P., Murfuni, M.S., Gaspari, M., Giordano, F., Naimo, G.D. ... Catalano, S. (2025). Adipocyte‑derived extracellular vesicles sustain mitochondrial metabolism in breast cancer cells: New insights into the cross‑talk between cancer cells and the tumor microenvironment. International Journal of Oncology, 67, 100. https://doi.org/10.3892/ijo.2025.5806
MLA
Gelsomino, L., Del Console, P., Murfuni, M. S., Gaspari, M., Giordano, F., Naimo, G. D., Fiorillo, M., Arpino, G., Giuliano, M., Panza, S., Bonofiglio, D., Andò, S., Barone, I., Giordano, C., Catalano, S."Adipocyte‑derived extracellular vesicles sustain mitochondrial metabolism in breast cancer cells: New insights into the cross‑talk between cancer cells and the tumor microenvironment". International Journal of Oncology 67.6 (2025): 100.
Chicago
Gelsomino, L., Del Console, P., Murfuni, M. S., Gaspari, M., Giordano, F., Naimo, G. D., Fiorillo, M., Arpino, G., Giuliano, M., Panza, S., Bonofiglio, D., Andò, S., Barone, I., Giordano, C., Catalano, S."Adipocyte‑derived extracellular vesicles sustain mitochondrial metabolism in breast cancer cells: New insights into the cross‑talk between cancer cells and the tumor microenvironment". International Journal of Oncology 67, no. 6 (2025): 100. https://doi.org/10.3892/ijo.2025.5806
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team