Cellular stress on angiogenesis modulation: Biological significance of extracellular vesicles

• Grant number: 16/19968-3
• Support Opportunities: Scholarships abroad - Research
• Start date: July 10, 2017
• End date: July 09, 2018
• Field of knowledge: Biological Sciences - Morphology - Cytology and Cell Biology
• Principal Investigator: Vanessa Morais Freitas
• Grantee: Vanessa Morais Freitas
• Host Investigator: Luisa Iruela-Arispe
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: University of California, Los Angeles (UCLA), United States

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.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

HILFENHAUS, GEORG; MOMPEON, ANA; FRESHMAN, JONATHAN; PRAJAPATI, DIVYA P.; HERNANDEZ, GLORIA; FREITAS, VANESSA M.; MA, FEIYANG; LANGENBACHER, ADAM D.; MIRKOV, SNEZANA; SONG, DANA; et al. A High-Content Screen Identifies Drugs That Restrict Tumor Cell Extravasation across the Endothelial Barrier. Cancer Research, v. 81, n. 3, p. 619-633, FEB 1 2021. (16/19968-3)