Fibroblast activation protein-α, a stromal cell surface protease, shapes key features of cancer associated fibroblasts through proteome and degradome alterations

Cancer associated fibroblasts (CAFs) constitute an abundant stromal component of most solid tumors. Fibroblast activation protein (FAP) α is a cell surface protease that is expressed by CAFs. We corroborate this expression profile by immunohistochemical analysis of colorectal cancer specimens. To better understand the tumor-contextual role of FAPα, we investigate how FAPα shapes functional and proteomic features of CAFs using loss- and gain-of function cellular model systems. FAPα activity has a strong impact on the secreted CAF proteome (“secretome”), including reduced levels of anti-angiogenic factors, elevated levels of transforming growth factor (TGF) β, and an impact on matrix processing enzymes.

Source: Molecular Oncology - August 11, 2015 Category: Cancer & Oncology Authors: M.M. Koczorowska, S. Tholen, F. Bucher, L. Lutz, J.M. Kizhakkedathu, O. De Wever, U. Wellner, M.L. Biniossek, A. Stahl, S. Lassmann, O. Schilling Source Type: research