Involvement of proteasomes in migration and matrix metalloproteinase-9 production of oral squamous cell carcinoma

✍ Scribed by Tetsuro Ikebe; Hiroshi Takeuchi; Eijiro Jimi; Mahiro Beppu; Masanori Shinohara; Kanemitsu Shirasuna

• Publisher: John Wiley and Sons
• Year: 1998
• Tongue: French
• Weight: 442 KB
• Volume: 77
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/(sici)1097-0215(19980812)77:4<578::aid-ijc18>3.0.co;2-2

✦ Synopsis

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 ␣ (TNF␣), 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 TNF␣-induced migration through gelatin appeared to be associated with the gelatinolytic activity from the cells, since TNF␣ 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-B, which is known to regulate MMP-9 expression in TNF␣-stimulated SCC cells. The TNF␣-induced degradation of IB␣ was also suppressed by ALLN treatment, thus implying that the molecule linking proteasome to MMP-9 production should be IB␣. We finally reconfirmed the involvement of proteasomes in the invasive behavior of oral SCC using lactacystin, a specific proteasome inhibitor, which could prevent TNF␣ from enhancing MMP-9 production, NF-B activation, induction of MMP-9 mRNA and cell migration.