Fibroblast growth factors and their receptors in urological cancers: basic research and clinical implications

Abstract

Because therapeutical options for advanced urological cancers are limited, the understanding of key elements responsible for invasion and metastasis is very important. It has been hypothesized that progression to malignant growth is associated with a dysregulation of growth factors and/or their receptors. In the last few years, signaling pathways of the fibroblast growth factor (FGF) family have been subject to intense investigation. Fibroblast growth factors constitute one of the largest families of growth and differentiation factors for cells of mesodermal and neuroectodermal origin. The family comprises two prototypic members, acidic FGF (aFGF) and the basic FGF (bFGF), as well as 21 additionally related polypeptide growth factors that have been identified to date. FGFs are involved in many biological processes during embryonic development, wound healing, hematopoesis, and angiogenesis. In prostate, bladder, and renal cancers, FGFs regulate the induction of metalloproteinases (MMP) that degrade extracellular matrix proteins, thus facilitating tumor metastasis. Probably due to their potent angiogenic properties, aFGF and bFGF have received the most attention. However, there is increasing evidence that other FGFs also play crucial roles in tumors of the prostate, bladder, kidney, and testis. This review will discuss the different elements involved in FGF signaling and summarize the present knowledge of their biological and clinical relevance in urological cancers.