Endothelial cells provide a notch-dependent pro-tumoral niche for enhancing breast cancer survival, stemness and pro-metastatic properties

Pegah Ghiabi, Jie Jiang, Jennifer Pasquier, Mahtab Maleki, Nadine Abu-Kaoud, Shahin Rafii, Arash Rafii Tabrizi

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Treating metastasis has been challenging due to tumors complexity and heterogeneity. This complexity is partly related to the crosstalk between tumor and its microenvironment. Endothelial cells -the building blocks of tumor vasculature- have been shown to have additional roles in cancer progression than angiogenesis and supplying oxygen and nutrients. Here, we show an alternative role for endothelial cells in supporting breast cancer growth and spreading independent of their vascular functions. Using endothelial cells and breast cancer cell lines MDA-MB231 and MCF-7, we developed co-culture systems to study the influence of tumor endothelium on breast tumor development by both in vitro and in vivo approaches. Our results demonstrated that endothelial cells conferred survival advantage to tumor cells under complete starvation and enriched the CD44HighCD24Low/- stem cell population in tumor cells. Moreover, endothelial cells enhanced the prometastatic potential of breast cancer cells. The in vitro and in vivo results concordantly confirmed a role for endothelial Jagged1 to promote breast tumor through notch activation. Here, we propose a role for endothelial cells in enhancing breast cancer progression, stemness, and pro-metastatic traits through a perfusion-independent manner. Our findings may be beneficial in developing novel therapeutic approaches.

Original languageEnglish
Article numbere112424
JournalPLoS One
Volume9
Issue number11
DOIs
Publication statusPublished - 7 Nov 2014

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Endothelial cells
breast neoplasms
endothelial cells
Tumors
niches
Endothelial Cells
Breast Neoplasms
neoplasms
Neoplasms
Cells
Tumor Microenvironment
coculture
Coculture Techniques
Starvation
angiogenesis
endothelium
blood vessels
metastasis
Endothelium
cell viability

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Endothelial cells provide a notch-dependent pro-tumoral niche for enhancing breast cancer survival, stemness and pro-metastatic properties. / Ghiabi, Pegah; Jiang, Jie; Pasquier, Jennifer; Maleki, Mahtab; Abu-Kaoud, Nadine; Rafii, Shahin; Tabrizi, Arash Rafii.

In: PLoS One, Vol. 9, No. 11, e112424, 07.11.2014.

Research output: Contribution to journalArticle

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AU - Abu-Kaoud, Nadine

AU - Rafii, Shahin

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