The prospect of molecular targeted therapy for colon cancer applying keratinocyte growth factor receptor (KGFR) gene silencing.

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[Purpose] Twenty-two kinds of fibroblast growth factor (FGF), which contributes the cell growth and the angiogenesis, have been reported to the present. Among FGF group, FGF-7 (Keratinocyte Growth Factor, KGF) and FGF-10 (KGF-2) are mainly synthesized by mesen-chymal cells, and participate in proliferation of the epitherial cells. Their actions are dependent on their binding to a specific cell-surface KGF receptor (KGFR). This study was performed to clarify the growth inhibitory effects of antisense oligonucleotide and short interfering RNA (siRNA) for keratinocyte growth factor family (KGF, KGF-2, KGFR) on colon cancer cells.[Materials and Methods] The expression and localization of KGF, KGF-2 and KGFR in human colon cancer tissue and colon cancer cell lines were examined using RT-PCR, immunohistochemistry and in situ hybridization. The recombinant KGF and KGF-2 were administrated into colon cancer cells and growth effects were estimated. The antisense oligonucleotide for KGF and KGF-2 mRNA and the siRNA for KGFR were transferred into colon cancer cell lines and the each growth inhibitory effects were elucidated.[Results and Discussion] KGF and KGF-2 and their mRNAs were localized in fibroblasts and colon cancer cells. KGFR and its mRNA were localized in colon cancer cells. These findings indicate that KGF and KGF-2 may contribute to colon cancer cell growth via autocrine and paracrine mechanisms. But we failed to obtain a satisfactory result from the study of colon cancer cell growth suppression. It is doubtful that KGF affects the growth of colon cancer precipitately. On the other hand, the study of immunochemistry in colon cancer showed that no KGFR was found in poorly differentiated colon cancer, but it was found in many differentiated colon cancer. Therefore, it is suspected that the affect of KGF is intimately related to the formation of duct structure and its maintenance.