THE INFLUENCE OF G-CSF ON HEAD AND NECK CANCER, AND STRATEGY FOR TREATMENT USING MUTATED G-CSF RECEPTOR GENE

Abstract

Dysplasia and squamous cell carcinoma exhibited higher G-CSFR expression than normal and hyperplastic epithelium. There was a significant association between G-CSFR expression on cancer cells and a poor prognosis in patients with oral and oropharyngeal squamous cell carcinoma (SCC), suggesting that the expression of G-CSFR in oral and oropharyngeal SCC may be a independent prognostic factor. Reconbinant G-CSF (rG-CSF) enhanced the invasive potentiality of head and neck cell lines. The binding of rG-CSF to G-CFSR induced phosphrylation of JAK and enhancedtype IV collagenase activity. The experiment of in vitro G-CSFR gene transfection also showed that rG-CSF significantly augmented their invasive potential in cancer cells. It was sugested that rG-CSF may activate p38 MAP kinase and increse nulear trascriptional factor in cancer cells, by DNA microarray analysis. No unusual isoforms were found in head and neck cancer cel lines. Dominant negative transfection using mutated G-CSFR decresed the enhancement of MT-MMP expression induced by G-CSF.