Studying Breast Cancer Metastasis Via the Effect of Breast Cancer Cells on Endothelial Cells

Metastasis, the phenomenon by which cancer cells spread from a primary tumor to distant organs, is greatly influenced by endothelial cells, which provide tumors with the oxygen and nutrients that they need to survive and spread. In this study, we analyzed cell proliferation rates of human umbilical vein endothelial cells (HUVECs), lymphatic endothelial cells (LECs), and microvascular endothelial cells (MECs) when co-cultured (CC) or cultured with conditioned media (CM) from MCF7, SKBR3, and MDAMB231 breast cancer cells. Cell proliferation was determined using a fluorescence assay and was quantified on days 1 and 4 of the experiment. We found that in LEC-CM and HUVEC-CM experiments, the more metastatic cancer cell lines increased cell proliferation as compared to control. In HUVEC-CC, MEC-CC and MEC-CM, all cell lines showed an inhibitory effect on endothelial cell proliferation, and in LEC-CC, MDAMB231 cells showed decreased cell proliferation as compared to other cancer cell lines. Very different trends in cell proliferation were seen for conditioned media versus co-culture conditions and, therefore, we can conclude that conditioned media and co-culture conditions do affect endothelial cells in different ways. In co-culture, growth factors secreted by the cancer cells can cause paracrine factor secretion by the endothelial cells, which could then stimulate a cyclic crosstalk between them that is not seen in conditioned media experiments. The results of this study will be used to correlate endothelial cell proliferation, among other phenotypes associated with cancer progression, with the associated metabolic profiles of the endothelial cells. The broader aim of this project is to link specific metabolic pathways and related regulation of specific factors to the physical behavior of the cells. This could lead to more effective clinical treatments for breast cancer through the targeting of endothelial cell functions critical for cancer cell survival.