Molecular and biological analysis of the mechanisms of impaired wound healing in gastrointestinal tract.-The role of fibroblast growth factor receptor 3-IIIb.

点击翻译按钮获取中文摘要

The initial purpose of the study was to analyze the functional role of Fibroblast Growth Factor Receptor 3-IlIb (FGFR3-IIIb), which has been shown to be expressed specifically by colonic epithelial cells, in the process of normal or impaired wound healing of gastrointestinal tract and found that the contribution of the receptor to epithelial wound healing was not significant. We alternatively investigate whether a change in the gene expression and splice variations of FGFR3 is associated with malignant progression in human gastrointestinal cancers. First, we examined the gene expression of FGFR3 isoforms in human esophageal, gastric, and colorectal cancer patients by RT-PCR. FGFR3 has three alternatively spliced isoforms. FGFR3-IIIb and FGFR3-ILIc are the transmembrane -type isoforms and have different ligand specificities. The third isoform, FGFR3ΔTM, is the soluble isoform lacking the transmembrane domain and secreted extracellularly. The incidence of FGFR3-IIIc in the esophageal carcinoma was significantly higher than in the normal human esophageal biopsies. In contrast, FGFR3-IIIb and FGFR3ΔTM were significantly increased in the colorectal carcinomas compared to the normal tissue from the same patients. Next, we investigated the importance of FGFR3-IIIc in epithelial cancer cells. We showed that the ecdysone-inducible expression of FGFR3-IIIc in human squamous cell carcinoma DJM1 cells greatly enhanced anchorage-dependent and -independent growth, and wound healing in response to FGF2. Thus, FGFR3c has the potential to enhance malignant progression in epithelial cancers. Although the physiological significance of FGFR3ΔΔTM has not yet been defined, our findings suggest that the increased expression of FGFR3-IIIc together with FGFR3-IIIb and FGFR3ΔATM may be important markers for malignancy and potential anti-cancer therapeutic targets in gastrointestinal cancers.