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
April 2013 Volume 42 Issue 4

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
April 2013 Volume 42 Issue 4

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
Article

Human mesenchymal stem cells enhance autophagy of lung carcinoma cells against apoptosis during serum deprivation

  • Authors:
    • Ming-Hui Zhang
    • Yi-De Hu
    • Yu Xu
    • Yu Xiao
    • Yan Luo
    • Zong‑Chang Song
    • Jing Zhou
  • View Affiliations / Copyright

    Affiliations: The Third Department of Oncology, PLA Cancer Research Institute of the Second Affiliated Hospital, The Third Military Medical University, Chongqing 400037, P.R. China
  • Pages: 1390-1398
    |
    Published online on: February 6, 2013
       https://doi.org/10.3892/ijo.2013.1810
  • 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

Currently, some evidence suggests that human multipotential mesenchymal stems cells (hMSCs) aid tumor growth and metastasis. Nutrient deprivation and oxygen deficiency are representative characteristics of solid tumor microenvironment during the cancer development. Because the effects of hMSCs on tumors under stressful conditions have not been determined, we investigated the survival mechanisms used by stressed stromal cells on A549 and SPC-1 lung carcinoma cell lines in vitro and in vivo. An indirect culture system was used to investigate the effects of hMSCs on viability and apoptosis in starved carcinoma cells and focused on the role of autophagy in regulating the survival of carcinoma cells. The results showed that A549 and SPC-1 cells had higher viability when co-cultured with hMSCs and that this was mainly attributed to decreased apoptosis. Autophagosomes were analyzed using GFP-LC3 and electron microscopy, which showed that autophagy was significantly activated in the starved co-culture groups. However, the inhibition of autophagy by the autophagic inhibitor 3-MA significantly abrogated the apoptosis reduction in either single groups or co-culture groups under serum deprivation, which implied that the hMSCs protected against apoptosis by enhancing autophagy in lung carcinoma cells in vitro. We also observed that hMSCs promoted tumor initiation and growth in vivo. In conclusion, our study demonstrates that hMSCs can protect carcinoma cells from nutrient deprivation-induced apoptosis and promote tumor initiation and growth, and, interestingly, autophagy plays an important role in the survival of cancer cells.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

View References

1 

Siegel R, Desantis C, Virgo K, et al: Cancer treatment and survivorship statistics, 2012. CA Cancer J Clin. 62:220–241. 2012. View Article : Google Scholar : PubMed/NCBI

2 

Prockop DJ: Marrow stromal cells as stem cells for nonhematopoietic tissues. Science. 276:71–74. 1997. View Article : Google Scholar : PubMed/NCBI

3 

Young HE, Steele TA, Bray RA, et al: Human reserve pluripotent mesenchymal stem cells are present in the connective tissues of skeletal muscle and dermis derived from fetal, adult, and geriatric donors. Anat Rec (Hoboken). 264:51–62. 2001. View Article : Google Scholar

4 

Pittenger MF, Mackay AM, Beck SC, et al: Multilineage potential of adult human mesenchymal stem cells. Science. 284:143–147. 1999. View Article : Google Scholar : PubMed/NCBI

5 

Young HE, Duplaa C, Young TM, et al: Clonogenic analysis reveals reserve stem cells in postnatal mammals: I. Pluripotent mesenchymal stem cells. Anat Rec (Hoboken). 263:350–360. 2001. View Article : Google Scholar : PubMed/NCBI

6 

Fox JM, Chamberlain G, Ashton BA and Middleton J: Recent advances into the understanding of mesenchymal stem cell trafficking. Br J Haematol. 137:491–502. 2007. View Article : Google Scholar : PubMed/NCBI

7 

Karnoub AE, Dash AB, Vo AP, et al: Mesenchymal stem cells within tumour stroma promote breast cancer metastasis. Nature. 449:557–563. 2007. View Article : Google Scholar : PubMed/NCBI

8 

Mishra PJ, Humeniuk R, Medina DJ, et al: Carcinoma-associated fibroblast-like differentiation of human mesenchymal stem cells. Cancer Res. 68:4331–4339. 2008. View Article : Google Scholar : PubMed/NCBI

9 

Studeny M, Marini FC, Champlin RE, Zompetta C, Fidler IJ and Andreeff M: Bone marrow-derived mesenchymal stem cells as vehicles for interferon-beta delivery into tumors. Cancer Res. 62:3603–3608. 2002.PubMed/NCBI

10 

Xin H, Kanehira M, Mizuguchi H, et al: Targeted delivery of CX3CL1 to multiple lung tumors by mesenchymal stem cells. Stem Cells. 25:1618–1626. 2007. View Article : Google Scholar : PubMed/NCBI

11 

Stagg J: Mesenchymal stem cells in cancer. Stem Cell Rev. 4:119–124. 2008. View Article : Google Scholar : PubMed/NCBI

12 

Zhang W: Mesenchymal stem cells in cancer: friends or foes. Cancer Biol Ther. 7:252–254. 2008. View Article : Google Scholar : PubMed/NCBI

13 

Bian ZY, Fan QM, Li G, Xu WT and Tang TT: Human mesenchymal stem cells promote growth of osteosarcoma: involvement of interleukin-6 in the interaction between human mesenchymal stem cells and Saos-2. Cancer Sci. 101:2554–2560. 2010. View Article : Google Scholar : PubMed/NCBI

14 

Bagley RG, Weber W, Rouleau C, et al: Human mesenchymal stem cells from bone marrow express tumor endothelial and stromal markers. Int J Oncol. 34:619–627. 2009. View Article : Google Scholar : PubMed/NCBI

15 

Kato K, Ogura T, Kishimoto A, et al: Critical roles of AMP-activated protein kinase in constitutive tolerance of cancer cells to nutrient deprivation and tumor formation. Oncogene. 21:6082–6090. 2002. View Article : Google Scholar : PubMed/NCBI

16 

Li Y, Iglehart JD, Richardson AL and Wang ZC: The amplified cancer gene LAPTM4B promotes tumor growth and tolerance to stress through the induction of autophagy. Autophagy. 8:273–274. 2012. View Article : Google Scholar : PubMed/NCBI

17 

Kelekar A: Introduction to the review series Autophagy in Higher Eukaryotes--a matter of survival or death. Autophagy. 4:555–556. 2008. View Article : Google Scholar : PubMed/NCBI

18 

Yin L, Kharbanda S and Kufe D: MUC1 oncoprotein promotes autophagy in a survival response to glucose deprivation. Int J Oncol. 34:1691–1699. 2009.PubMed/NCBI

19 

Carew JS, Medina EC, Esquivel JA II, et al: Autophagy inhibition enhances vorinostat-induced apoptosis via ubiquitinated protein accumulation. J Cell Mol Med. 14:2448–2459. 2010. View Article : Google Scholar

20 

Kang C, You YJ and Avery L: Dual roles of autophagy in the survival of Caenorhabditis elegans during starvation. Genes Dev. 21:2161–2171. 2007. View Article : Google Scholar : PubMed/NCBI

21 

Mathew R, Karantza-Wadsworth V and White E: Role of autophagy in cancer. Nature reviews Cancer. 7:961–967. 2007. View Article : Google Scholar

22 

Fujii S, Mitsunaga S, Yamazaki M, et al: Autophagy is activated in pancreatic cancer cells and correlates with poor patient outcome. Cancer Sci. 99:1813–1819. 2008.PubMed/NCBI

23 

Dominici M, Le Blanc K, Mueller I, et al: Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy. 8:315–317. 2006. View Article : Google Scholar

24 

Rhodes LV, Muir SE, Elliott S, et al: Adult human mesenchymal stem cells enhance breast tumorigenesis and promote hormone independence. Breast Cancer Res Treat. 121:293–300. 2010. View Article : Google Scholar : PubMed/NCBI

25 

Klionsky DJ, Abeliovich H, Agostinis P, et al: Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes. Autophagy. 4:151–175. 2008. View Article : Google Scholar

26 

Seglen PO and Gordon PB: 3-Methyladenine: specific inhibitor of autophagic/lysosomal protein degradation in isolated rat hepatocytes. Proc Natl Acad Sci USA. 79:1889–1892. 1982. View Article : Google Scholar : PubMed/NCBI

27 

Sanchez CG, Penfornis P, Oskowitz AZ, et al: Activation of autophagy in mesenchymal stem cells provides tumor stromal support. Carcinogenesis. 32:964–972. 2011. View Article : Google Scholar : PubMed/NCBI

28 

Degenhardt K, Mathew R, Beaudoin B, et al: Autophagy promotes tumor cell survival and restricts necrosis, inflammation, and tumorigenesis. Cancer Cell. 10:51–64. 2006. View Article : Google Scholar : PubMed/NCBI

29 

Karantza-Wadsworth V and White E: Role of autophagy in breast cancer. Autophagy. 3:610–613. 2007. View Article : Google Scholar

30 

Lum JJ, Bauer DE, Kong M, et al: Growth factor regulation of autophagy and cell survival in the absence of apoptosis. Cell. 120:237–248. 2005. View Article : Google Scholar : PubMed/NCBI

31 

Karantza-Wadsworth V, Patel S, Kravchuk O, et al: Autophagy mitigates metabolic stress and genome damage in mammary tumorigenesis. Genes Dev. 21:1621–1635. 2007. View Article : Google Scholar : PubMed/NCBI

32 

Boya P, Gonzalez-Polo RA, Casares N, et al: Inhibition of macro-autophagy triggers apoptosis. Mol Cell Biol. 25:1025–1040. 2005. View Article : Google Scholar : PubMed/NCBI

33 

Roorda BD, ter Elst A, Kamps WA and de Bont ES: Bone marrow-derived cells and tumor growth: contribution of bone marrow-derived cells to tumor micro-environments with special focus on mesenchymal stem cells. Crit Rev Oncol Hematol. 69:187–198. 2009. View Article : Google Scholar : PubMed/NCBI

34 

Tian LL, Yue W, Zhu F, Li S and Li W: Human mesenchymal stem cells play a dual role on tumor cell growth in vitro and in vivo. J Cell Physiol. 226:1860–1867. 2011. View Article : Google Scholar : PubMed/NCBI

35 

Sinha S and Levine B: The autophagy effector Beclin 1: a novel BH3-only protein. Oncogene. 27(Suppl 1): S137–S148. 2008. View Article : Google Scholar : PubMed/NCBI

36 

Maiuri MC, Criollo A, Tasdemir E, et al: BH3-only proteins and BH3 mimetics induce autophagy by competitively disrupting the interaction between Beclin 1 and Bcl-2/Bcl-X(L). Autophagy. 3:374–376. 2007. View Article : Google Scholar

37 

Pattingre S, Tassa A, Qu X, et al: Bcl-2 antiapoptotic proteins inhibit Beclin 1-dependent autophagy. Cell. 122:927–939. 2005. View Article : Google Scholar : PubMed/NCBI

38 

Chang NC, Nguyen M, Germain M and Shore GC: Antagonism of Beclin 1-dependent autophagy by BCL-2 at the endoplasmic reticulum requires NAF-1. EMBO J. 29:606–618. 2010. View Article : Google Scholar : PubMed/NCBI

39 

Lian J, Wu X, He F, et al: A natural BH3 mimetic induces autophagy in apoptosis-resistant prostate cancer via modulating Bcl-2-Beclin1 interaction at endoplasmic reticulum. Cell Death Differ. 18:60–71. 2011. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Zhang M, Hu Y, Xu Y, Xiao Y, Luo Y, Song ZC and Zhou J: Human mesenchymal stem cells enhance autophagy of lung carcinoma cells against apoptosis during serum deprivation. Int J Oncol 42: 1390-1398, 2013.
APA
Zhang, M., Hu, Y., Xu, Y., Xiao, Y., Luo, Y., Song, Z., & Zhou, J. (2013). Human mesenchymal stem cells enhance autophagy of lung carcinoma cells against apoptosis during serum deprivation. International Journal of Oncology, 42, 1390-1398. https://doi.org/10.3892/ijo.2013.1810
MLA
Zhang, M., Hu, Y., Xu, Y., Xiao, Y., Luo, Y., Song, Z., Zhou, J."Human mesenchymal stem cells enhance autophagy of lung carcinoma cells against apoptosis during serum deprivation". International Journal of Oncology 42.4 (2013): 1390-1398.
Chicago
Zhang, M., Hu, Y., Xu, Y., Xiao, Y., Luo, Y., Song, Z., Zhou, J."Human mesenchymal stem cells enhance autophagy of lung carcinoma cells against apoptosis during serum deprivation". International Journal of Oncology 42, no. 4 (2013): 1390-1398. https://doi.org/10.3892/ijo.2013.1810
Copy and paste a formatted citation
x
Spandidos Publications style
Zhang M, Hu Y, Xu Y, Xiao Y, Luo Y, Song ZC and Zhou J: Human mesenchymal stem cells enhance autophagy of lung carcinoma cells against apoptosis during serum deprivation. Int J Oncol 42: 1390-1398, 2013.
APA
Zhang, M., Hu, Y., Xu, Y., Xiao, Y., Luo, Y., Song, Z., & Zhou, J. (2013). Human mesenchymal stem cells enhance autophagy of lung carcinoma cells against apoptosis during serum deprivation. International Journal of Oncology, 42, 1390-1398. https://doi.org/10.3892/ijo.2013.1810
MLA
Zhang, M., Hu, Y., Xu, Y., Xiao, Y., Luo, Y., Song, Z., Zhou, J."Human mesenchymal stem cells enhance autophagy of lung carcinoma cells against apoptosis during serum deprivation". International Journal of Oncology 42.4 (2013): 1390-1398.
Chicago
Zhang, M., Hu, Y., Xu, Y., Xiao, Y., Luo, Y., Song, Z., Zhou, J."Human mesenchymal stem cells enhance autophagy of lung carcinoma cells against apoptosis during serum deprivation". International Journal of Oncology 42, no. 4 (2013): 1390-1398. https://doi.org/10.3892/ijo.2013.1810
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