Heat shock suppresses membrane type 1-matrix metalloproteinase production and progelatinase a activation in human fibrosarcoma HT-1080 cells and thereby inhibits cellular invasion

Expression of membrane type-1 matrix metalloproteinase (MT1-MMP) is closely correlated with tumor invasiveness. We investigated the effect of hyperthe rmia on the production of MT1-MMP in human fibrosarcoma HT-1080 cells. Heat shock at 42 degrees C suppressed the production and gene expression of MT1 -MMP in HT-1080 cells. Heat shock-induced suppression of MT1-MMP production resulted in the inhibition of progelatinase A (proMMCP-2) activation and t he increased release of tissue inhibitor of metalloproteinases 2 from cell surface. In addition, in vitro tumor invasion assay in a Matrigel model ind icated that heat shock inhibited the invasive activity of HT-1080 cells. Th ese results suggest that heat shock preferentially suppresses the productio n of MT1-MMP and thereby inhibits proMMP-2 activation, events which subsequ ently inhibit tumor invasion. Therefore, heat shock shows an anti-invasive effect along with the known mechanism of inhibiting tumor growth. (C) 1999 Academic Press.