Emerging Role of Stromal Fibroblasts in Epithelial Cancer

Maria      Rita Rippo; Antonio      Procopio; Alfonso      Catalano

Abstract

The mechanisms involved in the tumor-stroma interaction during carcinoma progression are an area of intensive investigation. Cancer cells produce a range of growth factors and proteolytic enzymes that modify their stromal environment. These factors disrupt normal tissue homeostasis and act in a paracrine manner to induce angiogenesis and inflammation, as well as activation of surrounding stromal cell types such as fibroblasts, smooth-muscle cells and adipocytes, leading to the secretion of additional growth factors and proteases. Recent studies reveal that fibroblasts have more profound influence on the development and progression of carcinoma than was previously appreciated. These cancer-associated fibroblasts (CAFs) are a heterogeneous fibroblast population with different life-span which are activated and recruited during carcinoma progression. One of the more provocative implications is that genetically altered or/and senescence fibroblasts can induce epithelial cells to form carcinomas. In this article, we will review some evidences that CAFs produce a number of paracrine factors that affect several aspects of pleural and urothelial cancer progression. Moreover, we discuss how this new perspectives on the role of CAFs during cancer initiation and progression can have important implications to cancer therapy.

Keywords: CAFs, tumor stroma, myofibroblasts, pleural cancer, urothelial cancer