The Interplay between Atherosclerosis and Cancer: Breast Cancer Cells Increase the Expression of Endothelial Cell Adhesion Markers

SIMPLE SUMMARY: Cardiovascular diseases and cancer are the two most common causes of death worldwide. Although evidence shows a relationship between these two pathologies, there remain many unknown factors regarding their connection. We investigated the impact of the cancer environment on the initiation of atherosclerosis, which is a major contributor to cardiovascular diseases. We observed that the cancer cell medium influences the expression of markers involved in the adhesion of monocytes and endothelial cells, leading to the initiation of atherosclerosis. Additionally, we found that cancer cells have the capacity to oxidize low-density lipoproteins, thereby increasing the likelihood of cholesterol plaque formation in the arteries. In conclusion, our results suggest that cancer could promote atherosclerosis through the increased expression of endothelial cell markers and oxidation of low-density lipoproteins. These findings should be confirmed through clinical studies. ABSTRACT: Cardiovascular diseases are the leading causes of death worldwide, closely followed by cancer. To investigate the impact of breast cancer cell lines (SKBR3, MCF-7, and MDA-MB-231) on endothelial cell adhesion, a blended medium containing 30% breast-cancer-conditioned medium was prepared. This medium was then exposed to human umbilical vein endothelial cells (HUVECs) and monocytes (THP-1) for 48 h. Homemade oxidized low-density lipoproteins (oxLDL) were optionally added to the blended medium. Immunofluorescence was performed to assess the expression of E-selectin, connexin-43, and ICAM-1 on HUVECs, as well as LOX-1, CD36, and CD162 on THP-1. Additionally, unoxidized LDL was exposed to the three breast cancer cell lines for 48 h, and the formation of oxLDL was quantified. Our results revealed an upregulation of all six adhesion markers involved in the initiation of atherosclerosis when HUVECs and THP-1 were exposed to the breast-cancer-conditioned medium. Furthermore, this expression was further increased by exposure to oxLDL. We also observed a significant elevation in oxLDL levels when LDL was exposed to breast cancer cells. In conclusion, our findings successfully demonstrate an increased LDL oxidation in the presence of breast cancer cells, accompanied by an augmented expression of receptors involved in atherosclerosis initiation. These findings shed new light on the clinically observed interplay between atherosclerosis and cancer.