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 pro-metastatic 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.
Highlights
Breast cancer is the most commonly diagnosed cancer and the second cause of mortality in women in the western world [1]
Using a co-culture system to grow breast cancer cells (BCCs) and E4-Endothelial cells (ECs) jointly in a serum and cytokine-free environment, we showed that BCCs gained a pro-survival advantage through having contact with E4-ECs (Figure 1A–C)
We showed a new role for ECs in enhancing tumor development and progression
Summary
Breast cancer is the most commonly diagnosed cancer and the second cause of mortality in women in the western world [1]. Most breast cancer patients die due to tumor metastasis. Preventing breast cancer recurrence and metastasis seems challenging owing to disease complexity. In addition to tumor heterogeneity, this complexity can be in part attributed to the interaction between tumor cells and their microenvironment. The components of tumor microenvironment comprise of epithelial, endothelial, bone-marrow mesenchymal, and immune cells, as well as the elements of the extracellular matrix. The crosstalk between tumor cells and their surrounding microenvironment seems to be crucial for tumor growth, development, stemness, and metastatic spread [2]
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