EFFECT OF FLUID SHEAR STRESS ON TUMOR AND ENDOTHELIAL CELLS AND IN THE PROMOTION OF TUMOR-ENDOTHELIAL ADHESION

• Grant number: 23/04317-0
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: March 01, 2024
• End date: September 30, 2027
• Field of knowledge: Biological Sciences - Morphology - Cytology and Cell Biology
• Principal Investigator: Vanessa Morais Freitas
• Grantee: Sarah Eseroghene Najophe
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Breast cancer is the most common type of female cancer worldwide, with metastasis accounting for the majority of deaths, high recurrence, and poor prognosis rates. While not all of the mechanisms underlying the complex process of metastasis are fully understood, fluid shear stress, endothelial cells, and tumor-endothelial cell adhesions have all been implicated. Tumor cells adhere to endothelial cells in the vasculature via specific expressed receptors and ligands, and this interaction has a significant impact on tumor progression and metastasis to specific organs. Tumor cells in circulation are also subjected to fluid shear stress, which is the frictional force exerted by blood flow; however, the effect of fluid shear stress on tumor cells is debatable. While some studies claim that fluid shear stress eliminates tumor cells in the bloodstream, others claim that it promotes tumor invasion, extravasation, and thus metastasis. Furthermore, while studies have shown that endothelial cells are exposed to fluid shear stress and produce intracellular signals that may promote metastasis, more research is needed to determine the mechanisms by which these processes occur and how they are involved in metastasis. We will investigate the effect of fluid shear stress on tumor cells and endothelial cells to better understand the mechanisms of these processes and their roles in facilitating tumor cell survival and, thus, metastasis. We will look at proteins that are expressed differently in endothelial cells when they are exposed or not exposed to fluid shear stress, as well as the role of expressed proteins in endothelial cells using inhibitors and shRNAs. We will then investigate the role of fluid shear stress in promoting tumor-endothelial cell adhesions and, as a result, metastasis. Through this study, we hope to identify therapeutic targets that disrupt metastatic processes and improve patient treatment options.