Role of tumor-associated fibroblasts on the activity of potential anticancer compounds on lung and breast tumor cells in three-dimensional cell co-cultures

• Grant number: 19/25067-7
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: February 29, 2020
• End date: February 27, 2021
• Field of knowledge: Biological Sciences - Morphology - Cytology and Cell Biology
• Principal Investigator: Márcia Regina Cominetti
• Grantee: Angelina Maria Fuzer
• Supervisor: Jordi Alcaraz Casademunt
• Host Institution: Centro de Ciências Biológicas e da Saúde (CCBS). Universidade Federal de São Carlos (UFSCAR). São Carlos , SP, Brazil
• Institution abroad: Universitat de Barcelona (UB), Spain
• Associated to the scholarship: 17/01287-2 - Screening of candidates to new antitumoral drugs by three-dimensional cell culture, BP.PD

Abstract

Cancer is a leading cause of death worldwide. Lung and breast cancer are the most frequent cancer types. In vitro screening methods for antitumor candidate compounds represent a rapid, simple, and reproducible approach to obtain essential data indicative of activity and interaction of new molecules with potential cell targets. In vitro assays based on two-dimensional (2D) monolayer cultures are widely used, yet they are disadvantageous compared to three-dimensional (3D) cultures, which better mimic the in vivo tumor microenvironment. Within the heterogeneous tumor microenvironment, tumor cells interact not only with the extracellular matrix (ECM) but also with stromal cell types, such as macrophages, endothelial cells, and fibroblasts. Tumor associated fibroblasts (TAFs) are the most abundant stromal cell type and are essential to several steps of cancer progression and metastasis, including epithelial-mesenchymal transition, migration, invasion and angiogenesis through the aberrant secretion of growth factors, cytokines, extracellular vesicles, and ECM components. Importantly, there is growing evidence that TAFs can also modulate tumor responses to drugs and can even trigger drug-resistance. The host research group has pioneered the study of the role of lung TAFs and the responses and resistance to antiangiogenic and antifibrotic drugs. This project aims to learn new techniques to test the interference of TAFs in the effects of anticancer compounds that are studied in our group in Brazil as well as to assess the antifibrotic potential of these compounds to ultimately define their potential use in combined therapies with chemotherapy, radiotherapy and/or immunotherapy. (AU)