Abstract
Metastasis-associated protein 1 (MTA1) is physiologically expressed at only lowlevels in human tissue, except testis. Its expression has been found to be associated with progression in solid cancers of various organs and cancer cell lines with high invasive potential and thus is believed to play a role in cancer progression to the metastatic state. Functional studies supported this by showing that experimental overexpression of MTA1 in keratinocytes is associated with increase in migration and invasion and survival in the anchorage-independent state. However, few reports have examined the role of MTA1 in oral squamous cell carcinoma. To determine the relationship between clinicopathologic factors and MTA1 expression in patients with oral squamous cell carcinoma, we investigated MTA1 gene expression and protein production. 38 oral squamous cell carcinomas (tongue carcinoma) were enrolled in this study. The expression of MTA1 was assayed immunohistochemically using polyclonal antibodies, and the expression of PCNA was assayed immunohistochemically using monoclonal antibody. The human oral squamous cell carcinoma cell lines, SAS, HSC-2, OSC19 and OSC20 were obtained from the Human Science Research Resource Bank. For PCR analysis, cDNA was amplified by Taq DNA polymerase. BioCoat Matrigel invasion chambers were used to assess cell invasion. Briefly, cells were seeded in the upper chamber. Cells on the reverse side of the insert were fixed and stained with DiffQuick. To investigate the correlation of MTA1 with cancer invasion, the effect of MTA1 inhibition was examined by RNA interference (RNAi). Significance was assessed by means of Student T test and Pearsons correlation coefficient. MTA1 protein expression was detected in 33 of 38 SCCs. There was no correlation between MTA1 expression and T category. There was correlation between MTA1 expression and N category and clinical stage. Immunohistochemical expression of MTA1 had no correlation with tumor cell growth factor (PCNA) and WHO histological malignancy grade. MTA1 protein production was strongly associated with cancer cell invasion (p<0.05), and there was significant correlation with lymph node metastasis and MTA1 protein production. HSC2 revealed low mRNA expression and OSC 20 revealed highest mRNA expression. In matrigel invasion assay, the HSC2 cell line revealed lowest invasion and the OSC20 cell line revealed highest invasion. RNAi-mediated MTA1 reduction decreased the invasion index (p<0.01). MTA1 may be a useful marker for lymph node metastasis, and MTA1 expression may be associated with increased invasive ability in oral squamous cell carcinomas.
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