|Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2002: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2001: ¥3,000,000 (Direct Cost: ¥3,000,000)
Serine proteases have important roles in tumor invasion and metastasis and their inhibitors, serine protease inhibitors (serpins) are attractive targets for therapeutic strategies. On chromosome 18q21, which is recognized as a region for frequent loss of heterozygosity (LOH) in head and neck squamous cell carcinoma (HNSCC), there is a cluster of serping; maspin, headpin, and SCCA1. Others and we have reported that the expression of maspin, headpin and SCCA1 are down-regulated in HNSCC cells as compared to normal squamous epithelial cells. In this study, we hypothesized that expression of these serpins are biologically disadvantageous to HNSCC cells. We also hypothesized that alterations in these serpin expression will produce differences in the phenotypic behavior of oral SCC tumors in patients. Established HNSCC cell lines were stably transfected with a mammalian expression vector with SCCA1 or headpin cDNA. In vitro proliferation, migration, or invasive potential (Matrigel assay) of
the transfectans were assayed. In addition, archival paraffin embedded specimens of primary tongue tumors from patients were analyzed for SCCA1, maspin, and headpin mRNA and/or protein expression using quantitative RT-PCR and/or imunohistochemistry respectively. The relationship between the expression and invasiveness, clinical courses of the patients were analyzed. Headpin or SCCA1 expression did not alter the in vitro growth rate of established HNSCC cells. However, SCCA1 and headpin expression both significantly inhibited the in vitro invasion in matrigel assays. The absence of maspin expression in oral SCC specimens was found more frequently in cases of subsequent cervical lymph node metastasis than in cases without metastasis.
SCCA1 and headpin may function to inhibit the invasive potential of HNSCC. Loss of expression of 18q21 serpins; maspin, headpin and SCCA1 may play a role in the malignant progression of HNSCC.
Serpins which locate as 18q21; maspin, headpin and SCCA1 have potential to be the molecular targets in the treatment of HNSCC. Less