温熱刺激によるガン細胞のMT1-MMP発現抑制機構 : ガン温熱療法の新規有用性

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Expression of membrane type-1 matrix metalloproteinase (MT 1-MMP) is closely correlated with tumor invasiveness. We investigated the effect of hyperthermia on the production of MT 1-MMP in human tumor cells. Hyperthermia at 42℃ suppressed the production and gene expression of MT 1-MMP in human filbrosarcoma HT-1080 cells. Hyperthermia-induced suppression of MT 1-MMP production resulted in the inhibition of proMMP-2/progelatinase A activation and the increased release of tissue inhibitior-2 of metalloproteinases (TIMP-2) from cell surface. In addition, hyperthermia inhibited the in-vitro invasive activity of HT-1080 cells. These hyperthermic effects were also observed in human squamous carcinoma A 431 and SAS cells, but not in normal human fibroblasts. On the other hand, hypertermia induced a transient increase of intracellular cAMP level in tumor cells, but not in normal cells. A short-term treatment with forskolin mimicked the hyperthermic effects on MT 1-MMP-mediated proMMP-2 activation in tumor cells and thereby the inhibition of in-vitro tumor invasion. These results suggest that hyperthermia preferentially suppresses the production of MT 1-MMP and thereby inhibits proMMP-2 activation, which events subsequently inhibit tumor invasion, and that a transient increase in intracellular cAMP is a critical signal for hyperthermia to induce tumor specific-suppression of MT 1-MMP production and proMMP-2 activation.
日本結合組織学会の論文
2001-03-25

温熱刺激によるガン細胞のMT1-MMP発現抑制機構 : ガン温熱療法の新規有用性

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