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Involvement of proteasomes in migration and matrix metalloproteinase‐9 production of oral squamous cell carcinoma
Author(s) -
Ikebe Tetsuro,
Takeuchi Hiroshi,
Jimi Eijiro,
Beppu Mahiro,
Shinohara Masanori,
Shirasuna Kanemitsu
Publication year - 1998
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19980812)77:4<578::aid-ijc18>3.0.co;2-2
Subject(s) - lactacystin , proteasome , proteasome inhibitor , gelatinase , matrix metalloproteinase , leupeptin , tumor necrosis factor alpha , cell culture , microbiology and biotechnology , metalloproteinase , biology , chemistry , immunology , biochemistry , protease , enzyme , genetics
We investigated whether proteasomes were involved in the invasiveness of oral squamous cell carcinoma (SCC) cells. The migration of SCC cells through a gelatin‐coated membrane was enhanced with tumor necrosis factor α (TNFα), which was strongly inhibited by a peptide aldehyde, N‐acetyl‐Leu‐Leu‐norleucinal (ALLN), but not by its structurally related compound, N‐acetyl‐Leu‐Leu‐methioninal (ALLM). Since ALLN is a more potent inhibitor against proteasomal proteolysis than ALLM, cell migration inhibited by ALLN may thus likely depend on proteasomes. The TNFα‐induced migration through gelatin appeared to be associated with the gelatinolytic activity from the cells, since TNFα strongly enhanced the production of matrix metalloproteinase (MMP)‐9/gelatinase B in the SCC cells, as detected by gelatin zymography. The production of MMP‐9 was also inhibited by pretreatment with ALLN, but not ALLM, in a dose‐dependent manner. Moreover, ALLN could block the activation and nuclear translocation of a transcription‐activating factor, NF‐κB, which is known to regulate MMP‐9 expression in TNFα‐stimulated SCC cells. The TNFα‐induced degradation of IκBα was also suppressed by ALLN treatment, thus implying that the molecule linking proteasome to MMP‐9 production should be IκBα. We finally reconfirmed the involvement of proteasomes in the invasive behavior of oral SCC using lactacystin, a specific proteasome inhibitor, which could prevent TNFα from enhancing MMP‐9 production, NF‐κB activation, induction of MMP‐9 mRNA and cell migration. Int. J. Cancer 77:578–585, 1998. © 1998 Wiley‐Liss, Inc.