Involvement of breast cancer stem cells in tumor angiogenesis

Wang,Yu; Li,Chen; Li,Yuqiang; Zhu,Zhitu

doi:10.3892/ol.2017.7238

Involvement of breast cancer stem cells in tumor angiogenesis

Authors:
- Yu Wang
- Chen Li
- Yuqiang Li
- Zhitu Zhu
View Affiliations

Affiliations: Biobank, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning 121000, P.R. China, Department of Oncology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning 121000, P.R. China
Published online on: October 20, 2017 https://doi.org/10.3892/ol.2017.7238
Pages: 8150-8155

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The aim of the present study was to investigate the role of breast cancer stem cells (BCSCs) in the angiogenesis of breast cancer tumors. The expression levels of mutant p53, cluster of differentiation (CD)31, vascular endothelial factor (VEGF), in addition to human epidermal growth factor (HER)2, were detected in the blood vessels of human breast cancer (BC) tissue samples. CD44+/CD24‑/low cells were selected from single‑cell suspensions of BC tissues to assess the expression of CD31 and CD105, in addition to the ability of these cells to metabolize acetylated low‑density lipoprotein (Ac‑LDL). Furthermore, vascular‑like structures were observed histologically. Mutant p53, CD31 and VEGF were all expressed in these tissues. CD44+ cells comprised 7.5±2.6 and 94.3±4.7% of the cell population prior to and following sorting, respectively. CD24+ cells comprised 48.2±9.4 and 4.3±4% of the cell population prior to and following sorting, respectively. A low proportion of CD24+ cells corresponded to a high proportion of CD24‑/low cells. The percentages of CD105+ and CD31+ glomus cells in the mammary gland were 4.5±0.9 and 6.2±1.3%, respectively, and following passaging for three generations, these increased to 79.6±9.3 and 84.1±10.7%, respectively (P<0.05). Cells were cultured using an endothelial cell culture system, and they internalized DiL‑Ac‑LDL. Here, vascular endothelial cells formed vascular‑like structures, whereas the control group demonstrated no such structures. Overall, the results suggest that BCSCs‑derived endothelial cells may contribute to tumor angiogenesis.

View Figures

View References

1	Hong CS, Graham NA, Gu W, Camacho Espindola C, Mah V, Maresh EL, Alavi M, Bagryanova L, Krotee PA, Gardner BK, et al: MCT1 modulates cancer cell pyruvate export and growth of tumors that co-express MCT1 and MCT4. Cell Rep. 14:1590–1601. 2016. View Article : Google Scholar : PubMed/NCBI
2	Liu R, Shi P, Nie Z, Liang H, Zhou Z, Chen W, Chen H, Dong C, Yang R, Liu S and Chen C: Mifepristone suppresses basal triple-negative breast cancer stem cells by down-regulating KLF5 expression. Theranostics. 6:533–544. 2016. View Article : Google Scholar : PubMed/NCBI
3	Zhang J, Liu D, Feng Z, Mao J, Zhang C, Lu Y, Li J, Zhang Q, Li Q and Li L: MicroRNA-138 modulates metastasis and EMT in breast cancer cells by targeting vimentin. Biomed Pharmacother. 77:135–141. 2016. View Article : Google Scholar : PubMed/NCBI
4	Telang N: Putative cancer-initiating stem cells in cell culture models for molecular subtypes of clinical breast cancer. Oncol Lett. 10:3840–3846. 2015.PubMed/NCBI
5	Zhu A, Li Y, Song W, Xu Y, Yang F, Zhang W, Yin Y and Guan X: Antiproliferative Effect of Androgen Receptor Inhibition in Mesenchymal Stem-Like Triple-Negative Breast Cancer. Cell Physiol Biochem. 38:1003–1014. 2016. View Article : Google Scholar : PubMed/NCBI
6	Schulenburg A, Blatt K, Cerny-Reiterer S, Sadovnik I, Herrmann H, Marian B, Grunt TW, Zielinski CC and Valent P: Cancer stem cells in basic science and in translational oncology: can we translate into clinical application? J Hematol Oncol. 8:162015. View Article : Google Scholar : PubMed/NCBI
7	Xu L, Zhang L, Hu C, Liang S, Fei X, Yan N, Zhang Y and Zhang F: WNT pathway inhibitor pyrvinium pamoate inhibits the self-renewal and metastasis of breast cancer stem cells. Int J Oncol. 48:1175–1186. 2016. View Article : Google Scholar : PubMed/NCBI
8	Yu J, Zhang Y, Leung LH, Liu L, Yang F and Yao X: Efficacy and safety of angiogenesis inhibitors in advanced gastric cancer: A systematic review and meta-analysis. J Hematol Oncol. 18:1112016. View Article : Google Scholar
9	Goel G and Sun W: Ramucirumab, another anti-angiogenic agent for metastatic colorectal cancer in second-line setting-its impact on clinical practice. J Hematol Oncol. 8:922015. View Article : Google Scholar : PubMed/NCBI
10	Trivanović D, Jauković A, Krstić J, Nikolić S, Okić Djordjević I, Kukolj T, Obradović H, Mojsilović S, Ilić V, Santibanez JF and Bugarski D: Inflammatory cytokines prime adipose tissue mesenchymal stem cells to enhance malignancy of MCF-7 breast cancer cells via transforming growth factor-β1. IUBMB Life. 68:190–200. 2016. View Article : Google Scholar : PubMed/NCBI
11	Kasimir-Bauer S, Bittner AK, König L, Reiter K, Keller T, Kimmig R and Hoffmann O: Does primary neoadjuvant systemic therapy eradicate minimal residual disease? Analysis of disseminated and circulating tumor cells before and after therapy. Breast Cancer Res. 18:202016. View Article : Google Scholar : PubMed/NCBI
12	Mori M, Ito F, Shi L, Wang Y, Ishida C, Hattori Y, Niwa M, Hirayama T, Nagasawa H, Iwase A, et al: Ovarian endometriosis-associated stromal cells reveal persistently high affinity for iron. Redox Biol. 6:578–586. 2015. View Article : Google Scholar : PubMed/NCBI
13	Kanwar JR, Kamalapuram SK, Krishnakumar S and Kanwar RK: Multimodal iron oxide (Fe3O4)-saturated lactoferrin nanocapsules as nanotheranostics for real-time imaging and breast cancer therapy of claudin-low, triple-negative (ER(−)/PR(−)/HER2(−)). Nanomedicine (Lond). 11:249–268. 2016. View Article : Google Scholar : PubMed/NCBI
14	Sharma B, Varney ML, Saxena S, Wu L and Singh RK: Induction of CXCR2 ligands, stem cell-like phenotype, and metastasis in chemotherapy-resistant breast cancer cells. Cancer Lett. 372:192–200. 2016. View Article : Google Scholar : PubMed/NCBI
15	Xie J, Liu J, Liu H, Liang S, Lin M, Gu Y, Liu T, Wang D, Ge H and Mo SL: The antitumor effect of tanshinone IIA on anti-proliferation and decreasing VEGF/VEGFR2 expression on the human non-small cell lung cancer A549 cell line. Acta Pharm Sin B. 5:554–563. 2015. View Article : Google Scholar : PubMed/NCBI
16	Botelho MC and Alves H: Endothelial progenitor cells in breast cancer. Int J Immunother Cancer Res. 2:1–2. 2016.PubMed/NCBI
17	Teng L, Peng S, Guo H, Liang H, Xu Z, Su Y and Gao L: Conditioned media from human ovarian cancer endothelial progenitor cells induces ovarian cancer cell migration by activating epithelial-to-mesenchymal transition. Cancer Gene Ther. 22:518–523. 2015. View Article : Google Scholar : PubMed/NCBI
18	Amoury M, Kolberg K, Pham AT, Hristodorov D, Mladenov R, Di Fiore S, Helfrich W, Kiessling F, Fischer R, Pardo A, et al: Granzyme B-based cytolytic fusion protein targeting EpCAM specifically kills triple negative breast cancer cells in vitro and inhibits tumor growth in a subcutaneous mouse tumor model. Cancer Lett. 372:201–209. 2016. View Article : Google Scholar : PubMed/NCBI
19	Kong L, Guo S, Liu C, Zhao Y, Feng C, Liu Y, Wang T and Li C: Overexpression of SDF-1 activates the NF-κB pathway to induce epithelial to mesenchymal transition and cancer stem cell-like phenotypes of breast cancer cells. Int J Oncol. 48:1085–1094. 2016. View Article : Google Scholar : PubMed/NCBI
20	Liu Y, Zou T, Wang S, Chen H, Su D, Fu X, Zhang Q and Kang X: Genistein-induced differentiation of breast cancer stem/progenitor cells through a paracrine mechanism. Int J Oncol. 48:1063–1072. 2016.PubMed/NCBI
21	Yin X, Zhang BH, Zheng SS, Gao DM, Qiu SJ, Wu WZ and Ren ZG: Coexpression of gene Oct4 and Nanog initiates stem cell characteristics in hepatocellular carcinoma and promotes epithelial-mesenchymal transition through activation of Stat3/Snail signaling. J Hematol Oncol. 8:232015. View Article : Google Scholar : PubMed/NCBI
22	Chen Y, Cang S, Han L, Liu C, Yang P, Solangi Z, Lu Q, Liu D and Chiao JW: Establishment of prostate cancer spheres from a prostate cancer cell line after phenethyl isothiocyanate treatment and discovery of androgen-dependent reversible differentiation between sphere and neuroendocrine cells. Oncotarget. 7:26567–26579. 2016. View Article : Google Scholar : PubMed/NCBI
23	Wang R, Chadalavada K, Wilshire J, Kowalik U, Hovinga KE, Geber A, Fligelman B, Leversha M, Brennan C and Tabar V: Glioblastoma stem-like cells give rise to tumour endothelium. Nature. 468:829–833. 2010. View Article : Google Scholar : PubMed/NCBI
24	Liu L, Tong Q, Liu S, Cui J, Zhang Q, Sun W and Yang S: ZEB1 Upregulates VEGF Expression and Stimulates Angiogenesis in Breast Cancer. PLoS One. 11:e01487742016. View Article : Google Scholar : PubMed/NCBI
25	De Francesco EM, Pellegrino M, Santolla MF, Lappano R, Ricchio E, Abonante S and Maggiolini M: GPER mediates activation of HIF1α/VEGF signaling by estrogens. Cancer Res. 74:4053–4064. 2014. View Article : Google Scholar : PubMed/NCBI
26	Jaeger S, Min J, Nigsch F, Camargo M, Hutz J, Cornett A, Cleaver S, Buckler A and Jenkins JL: Causal Network Models for Predicting Compound Targets and Driving Pathways in Cancer. J Biomol Screen. 19:791–802. 2014. View Article : Google Scholar : PubMed/NCBI
27	Lekovic G, Drazin D, Mak AC and Schwartz MS: Cyberknife radiosurgery and concurrent intrathecal chemotherapy for leptomeningeal metastases: Case report of prolonged survival of a HER-2⁺ breast cancer patient status-post craniospinal irradiation. Cureus. 8:e4532016.PubMed/NCBI
28	Suyama K, Onishi H, Imaizumi A, Shinkai K, Umebayashi M, Kubo M, Mizuuchi Y, Oda Y, Tanaka M, Nakamura M and Katano M: CD24 suppresses malignant phenotype by downregulation of SHH transcription through STAT1 inhibition in breast cancer cells. Cancer Lett. 374:44–53. 2016. View Article : Google Scholar : PubMed/NCBI
29	Gangopadhyay S, Nandy A, Hor P and Mukhopadhyay A: Breast cancer stem cells: A novel therapeutic target. Clin Breast Cancer. 13:7–15. 2013. View Article : Google Scholar : PubMed/NCBI
30	Park MT, Oh ET, Song MJ, Kim WJ, Cho YU, Kim SJ, Han JY, Suh JK, Choi EK, Lim BU, et al: The radiosensitivity of endothelial cells isolated from human breast cancer and normal tissue in vitro. Microvasc Res. 84:140–148. 2012. View Article : Google Scholar : PubMed/NCBI