Cellular stress on angiogenesis modulation: Biological significance of extracellular vesicles

Abstract

Breast cancer is the 2nd most deadly cancer worldwide, the most frequent and lethal malignancies in the female population. During tumor progression, angiogenesis is stimulated by tumor cells and ensures the supply of nutrients and oxygen ensuring the sustained growth of tumor cells. Prior to the formation of these new vessels, the present conditions in the tumor microenvironment include acidosis, hypoxia, nutrient limitation and metastatic cells also suffer from absence of adhesive substrate. We believe that only those cells resistant to inhospitable conditions can survive and continue the tumor growth. In contrast, the conventionally in vitro model used in the study of cancer not faithfully reproduces the tumor microenvironment, since it has a neutral pH, normoxic, with nutrient media and plastic-dimensional substrates treated to facilitate cell adhesion. Our laboratory using PCR array, evaluated gene expression of breast tumor cells in different stress situations and observed the increased expression of genes involved in angiogenesis when tumor cells are cultured at acidic pH. Furthermore, we observed that tumor cells resistant to acidic pH, release more extracellular vesicles than control cells. These vesicles can carry information specific to the tumor microenvironment cells, including endothelial cells. We order to investigate whether the decrease in pH in tumor cell cultures might induce the formation of new vessels by neighboring cells (endothelial). This information will contribute to the understanding of angiogenesis in tumors, which can increase the chances we get new therapies to stop the progression of breast tumors.