纖維母細胞生長因子受器第三型對頭頸部鱗狀上皮細胞癌細 胞遷移與癌症病程的影響

Abstract

Head and neck squamous cell carcinoma (HNSCC) causes significantly high morbidity and mortality in Taiwan, but effective treatments remain lacking. Therefore, our specific aim is to identify novel therapeutic targets against the progression of HNSCC. Fibroblast growth factor receptor 3 (FGFR3), a tyrosine kinase receptor, is critical for embryogenesis, wound healing and angiogenesis. Its aberrant expression causes developmental disorders and several cancers, including multiple myeloma, bladder cancer and prostate cancer. Recent reports suggested that differential expression of FGFR3 isoforms was linked to tumor progression in colorectal and pancreatic cancers. However, whether and how FGFR3 contributes to HNSCC progression is not known. To answer these questions, we examined the expression levels of FGFR3 isoforms in HNSCC from patients of different clinical stages. We found that in late stages of HNSCC, the expression levels of FGFR3 went up slightly. Among the isoforms, FGFR3IIIc isoform was slightly decreased, but FGFR3IIIb isoform did not change during tumor progression. These results were different from previous reports about FGFR3 in other cancers. We therefore perturbed FGFR3 activities in HNSCC cell lines to observe their effects on cell migration. Our results showed that FGFR3 knockdown increased cell migration, and that FGFR3IIIb overexpression reduced cell motility and decreased ERK & AKT signaling. However, FGFR3IIIc manipulation showed no effects on cell migration. These results imply that FGFR3IIIb suppresses HNSCC progression. In the meantime, our results also revealed that (1) effects of FGFR inhibitors on cell migration were regulated by other receptor signaling, such as epithelial growth factor receptor (EGFR), and (2) FGFR2 inhibition reduced cell motility. Though these in vitro data were not totally consistent with clinical data, our findings suggest that FGFR3 has complicated interactions with FGFR2 and other signal transduction molecules. Further investigation is needed to clarify these puzzles