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 hyperthermia 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 (proMMP-2) activation and the increased release of tissue inhibitor of metalloproteinases 2 from cell surface. In addition, in vitro tumor invasion assay in a Matrigel model indicated that heat shock inhibited the invasive activity of HT-1080 cells. These results suggest that heat shock preferentially suppresses the production of MT1-MMP and thereby inhibits proMMP-2 activation, events which subsequently inhibit tumor invasion. Therefore, heat shock shows an anti-invasive effect along with the known mechanism of inhibiting tumor growth.
Sato
T
T
School of Pharmacy, Tokyo University of Pharmacy and Life Science, Horinouchi, Hachioji, Tokyo, 192-0392, Japan.
Sawaji
Y
Y
Matsui
N
N
Sato
H
H
Seiki
M
M
Mori
Y
Y
Ito
A
A
D003094:Collagen; D004338:Drug Combinations; D004789:Enzyme Activation; D004792:Enzyme Precursors / Q000378:metabolism*; D005354:Fibrosarcoma / Q000201:enzymology / Q000473:pathology; D018093:Gelatinases / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006358:Hot Temperature; D006801:Humans; D007797:Laminin; D020782:Matrix Metalloproteinases / Q000096:biosynthesis / Q000235:genetics*; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D011509:Proteoglycans; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured
D004338:Drug Combinations; D004792:Enzyme Precursors; D007797:Laminin; D011509:Proteoglycans; C059485:matrigel; D019716:Tissue Inhibitor of Metalloproteinase-2; D003094:Collagen; D018093:Gelatinases; D020782:Matrix Metalloproteinases; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases; C069860:progelatinase