Role of fibroblast growth factors and their receptors in pancreatic cancer and chronic pancreatitis.

The fibroblast growth factor (FGF) family is a group of homologous heparin-binding polypeptides that has been implicated in a variety of human neoplasms and presently includes 14 members. FGF signaling is mediated by a dual-receptor system, consisting of four high-affinity tyrosine kinase receptors, termed fibroblast growth factor receptors (FGFRs), and of low-affinity heparan sulfate proteoglycan receptors that enhance ligand presentation to the FGFRs. Several FGFs, including FGF-1, -2, -3, -4, -5, -6, and -7, and several FGFR variants, among them the 2 immunoglobulin-like form and the IIIc splice variant of FGFR-1 and the keratinocyte growth factor receptor, a splice variant of FGFR-2, are expressed in human pancreatic cancer cell lines and are overexpressed in human pancreatic cancers or in the pancreas of chronic pancreatitis and, therefore, may play important roles in the pathobiology of these pancreatic diseases. This review summarizes the current information on the involvement of the FGF family and their receptors in human pancreatic cancer and chronic pancreatitis.