Abstract 3962: Differential extracellular matrix remodeling induced by VEGF-A and TGF-β activated fibroblasts

Abstract

Abstract Introduction: Tumor progression is modulated by the presence within the tumor microenvironment of activated fibroblasts called cancer-associated fibroblasts (CAFs). CAFs exhibit an increase in the production of collagen (COL), tenascin C (TNC) and fibronectin (FN), resulting in a remodeling of the extracellular matrix (ECM) within the tumor mass. CAFs-derived ECM guides the cancer cells to migrate directionally increasing metastasis. TGF-β and VEGF-A are highly express in tumors and promote progression, however, their role in ECM remodeling is poorly understood. This study seeks to analyze the ECM protein remodeling mediated by TGF- β o VEGF-A activated fibroblasts. Materials and methods: In vitro and in vivo ECM protein remodeling mediated by TGF- β o VEGF-A activated fibroblasts was analyzed through expression of TNC, FN and COL using immunofluorescence and second harmonic generation (SHG); alignment and thickness of the fibers; Organoleptic invasion and 2D migration assay were conducted to study the effect of the stiffness of collagen gels generated by VEGF-A and TGF-β activated fibroblasts in the migration/invasion of tumor cells. Results and discussion: ECM derived from VEGF-A and TGF-β activated fibroblasts have differential ECM remodeling patterns, including differences in the secretion of TNC, FN, and COL; alignment and thickness of the fibers, and migration/invasion rate. These changes results in a differential stiffness of the ECM, which would alter the directional migration of cancer cells within tumor microenvironment. Citation Format: Muriel A. Nuñez, Javier Cerda-Infante, Francisco Nualart, Gustavo Cerda, Isabel M. Yussef, Viviana P. Montecinos. Differential extracellular matrix remodeling induced by VEGF-A and TGF-β activated fibroblasts [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3962.