Isolation of highly metastatic clone from human oral cancer cell line transfected active form rho gene and Identification of metastasis relation molecule.

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An activated ras of fos gene has been known to guide metastatic potential expression. Rho, which is one of the ras-like low molecular weight G proteins, may cause an enhancement of cell motility that is essentiality for invasion or metastasis of cancer by decreasing cellular adhesion abilities. The function and action mechanism of rho has been noted recently. Akedo et al. reported that an activated human rho increased invasion ability of rat ascites hepatoma cells into mesothelial cell monolayer in an in vitro experiment.In the other hand, there were few studies of cancer metastasis using oral cancer cell lines. We have searched tumorigenicity by transplanting humans oral cancer cell line in the back of nude mouse, but lymphnode metastasis was not recognized. Highly metastasizing experimental model of oral cancer is necessary for studies of metastasis of oral cancer. So, we transfected plasmid pcDSR αrhoval^<14> that was active form of rho gene into NOS-1, the oral cancer cell line established form the primary squamous cell carcinoma of the lower gingiva, in order to obtain stable transfectants. Further, we examined whether highly metastasizing tumor cell line to the lymph node could be established from these cells.Consequently, stable transfectants which expressed active human rhoA gene were obtained by cotransfecting pcDSR αrhoVal^<14> and drug resistance gene pSV2neo. These clones promoted cell motility 2 times larger than that of the control by a phagokinetic track assay. They were transplantable orthotopically in the tongue of nude mouse, but lymph node metastasis was not observed.In this study, the cell motility of the clones that expressed active form rhoA gene showed an enhancement, but they did not give the lymphogenous metastatic potential.