The fibroblastic coconspirator in cancer progression

Abstract

A remarkable change has occurred in the thinking about epithelial-derived cancer in recent years: From almost entirely focusing on oncogenes and tumor suppressor genes has come the realization that the tumor microenvironment is a coconspirator in the carcinogenic process. Many types of stromal cells, including fibroblasts, adipocytes, macrophages, mast cells, and cells of the vascular system, are crucial contributors to epithelial carcinogenesis. Here, we focus on the fibroblast's role in cancer progression and the molecules involved in the communications between the fibroblasts and the cancer cells, including fibroblast secreted protein 1 (FSP-1 or S100A4), transforming growth factor beta (TGF-beta), the chemokine CXCL-12 (stromal derived factor 1 alpha, SDF-1alpha), type I collagen, and matrix metalloproteinase 13 (MMP-13).

Figure 1

Molecular coconspirators of stromal-epithelial interactions during tumorigenesis. The cells in the tumor tissue communicate during tumor progression through the secretion of growth factors, chemokines, and cytokines. Shown here are examples of modulators of tumorigenesis that are secreted by one cell type and act on another through activation (arrows), inactivation (blocked lines), or proteolytic cleavage (chewing symbol).