nm23-h1 suppresses invasion of oral squamous cell carcinoma-derived cell lines without modifying matrix metalloproteinase-2 and matrix metalloproteinase-9 expression

nm23-N1 is a candidate gene for the suppression of cancer metastasis. Sever al studies on human breast, hepatocellular, gastric, ovarian, and colon car cinomas and melanomas have shown that reduced nm23-H1 expression was closel y related to metastatic progression with poor prognosis. However, the bioch emical mechanism by which nm23-H1 suppresses the metastasis has yet to be e lucidated. In this study, we analyzed the correlation between nm23 expressi on, cell motility, and the invasive abilities of six different oral squamou s cell carcinoma cell lines (HSC2, HSC3, HSC4, KB, OSC19, and OSC20). Reduc ed mRNA/protein expression of the nm23-H1 was observed in three cell lines (HSC2, HSC3, and HSC4). These cell lines exhibited increased cell motility and an invasive character on organotypic raft culture. On the other hand, t he cell lines (KB, OSC19, and OSC20) that showed a higher expression of nm2 3-H1 exhibited a threefold to fivefold reduced motility and also reflected fewer invasions compared to the former three cell lines. Because the HSCS c ells demonstrated the lowest nm23-H1 expression with the highest cell motil ity and invasive character, we established nm23-H1-transfected NSCS cell li nes to investigate whether exogenous nm23-H1 protein could inhibit cell mig ration and invasive activity. These transfectants showed a significant redu ction in cell motility with exogenous nn23-H1 in a dose-dependent manner, a nd exhibited a noninvasive character. An immunofluorescence study demonstra ted a distinct stress-fiber distribution at peripheral region of these tran sfectants, However, no significant difference of matrix metalloproteinase ( MMP)-2 and MMP-9 expression was observed between mock transfectant and nm23 -H1-transfected cells. These findings suggest that nm23-H1 inhibits the inv asive activity of oral squamous cell carcinoma by suppression of cell motil ity without altering the MMP-2 and MMP-9 status.