%0 Journal Article
%T Fibroblast Growth Factor Receptor 2: Expression, Roles, and Potential As a Novel Molecular Target for Colorectal Cancer
%A Yoko Matsuda
%A Junji Ueda
%A Toshiyuki Ishiwata
%J Pathology Research International
%D 2012
%I Hindawi Publishing Corporation
%R 10.1155/2012/574768
%X The fibroblast growth factor receptor (FGFR) family consists of four members, named FGFR1, 2, 3, and 4. All 4 FGFRs and their ligands, fibroblast growth factors (FGFs), are expressed in colorectal cancer (CRC). Recent studies have shown that FGFR2 plays important roles in cancer progression; therefore, it is of great interest as a novel target for cancers. Expression of FGFR2 regulates migration, invasion, and growth in CRC. Expression of the FGFR2 isoform FGFR2 IIIb was associated with well-differentiated histological types, and its specific ligand, FGF7, enhanced angiogenesis and adhesion to type-IV collagen via FGFR2 IIIb in CRC. FGFR2 IIIc is detected in CRC, but its roles have not been well elucidated. Interactions between FGFR2 IIIb and IIIc and FGFs may play important roles in CRC via autocrine and/or paracrine signaling. Several kinds of molecular-targeting agents against FGFR2 have been developed; however, it is not clear how a cancer treatment can most effectively inhibit FGFR2 IIIb or FGFR2 IIIc, or both isoforms. The aim of this paper is to summarize the roles of FGFR2 and its isoforms in CRC and clarify whether they are potent therapeutic targets for CRC. 1. Introduction Colorectal cancer (CRC) is the second leading cause of death from cancer in the USA [1] and one of the most serious causes of death from cancer in the world. The prognosis remains poor, especially for patients with advanced or recurrent states of CRC. To improve the survival rates of patients with advanced stages, several types of anticancer, molecular-targeted agents have been developed and are currently undergoing clinical trials [2]. The fibroblast growth factors (FGFs) are heparin-binding growth factors and are classified as FGF-1 to FGF-23 [3¨C5]. Human FGFs, which comprise ~150¨C300 amino acids, have a conserved ~120 amino acid residue core, containing ~30¨C60% amino acid identity [4]. Patients with CRC have been reported to overexpress FGF-1 (acidic FGF), FGF-2 (basic FGF), FGF-3, FGF-7 (keratinocyte growth factor/KGF), FGF-9, FGF-10, FGF-18, FGF-19, and FGF-20. FGFs exert their biological activities by binding to high-affinity tyrosine kinase FGF receptors (FGFRs) on the surface of cells and low-affinity heparan sulfate proteoglycans that enhance ligand presentation [4]. FGFRs consist of four members, named FGFR1, 2, 3, and 4, that are encoded by distinct genes. FGFRs are single transmembrane receptors, containing extracellular, transmembrane, and intracellular domains. The extracellular domain of FGFRs is usually composed of 3 immunoglobulin-like domains (I-III).
%U http://www.hindawi.com/journals/pri/2012/574768/