Expression and Tissue Localization of Membrane-Types 1, 2, and 3 Matrix Metalloproteinases in Human Urothelial Carcinomas

No AccessJournal of UrologyInvestigative Urology1 Oct 1998EXPRESSION AND TISSUE LOCALIZATION OF MEMBRANE-TYPES 1, 2, AND 3 MATRIX METALLOPROTEINASES IN HUMAN UROTHELIAL CARCINOMAS YASHUHIDE KITAGAWA, KAZUTO KUNIMI, HIDEAKI ITO, HIROSHI SATO, TADAO UCHIBAYASHI, YASUNORI OKADA, MOTOHARU SEIKI, and MIKIO NAMIKI YASHUHIDE KITAGAWAYASHUHIDE KITAGAWA More articles by this author , KAZUTO KUNIMIKAZUTO KUNIMI Requests for reprints: Department of Urology, Kanazawa University School of Medicine, Takara-machi, 13-1, Kanazawa, 920 Japan. More articles by this author , HIDEAKI ITOHIDEAKI ITO More articles by this author , HIROSHI SATOHIROSHI SATO More articles by this author , TADAO UCHIBAYASHITADAO UCHIBAYASHI More articles by this author , YASUNORI OKADAYASUNORI OKADA More articles by this author , MOTOHARU SEIKIMOTOHARU SEIKI More articles by this author , and MIKIO NAMIKIMIKIO NAMIKI More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(01)62609-0AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: Three different membrane-type matrix metalloproteinases (MT1, 2, 3-MMP) which can activate proMMP-2 (progelatinase A) are thought to have an important role in various human carcinoma invasions and metastases. We examined the mRNA expression of MT-MMPs and the tissue immunolocalization of MT1-MMP in human urothelial carcinomas. Materials and Methods: mRNA was extracted from 27 clinical urothelial carcinomas and 10 normal urothelial mucosa tissues remote from the tumor. RT-PCR using specific primers was performed, and PCR products were hybridized to32 P-labeled internal probes and analyzed by a bioimage analyzer. Immunolocalization was studied using a monoclonal antibody against MT1-MMP (114-6G6). Results: MT1-MMP and MT2-MMP mRNA expressions in urothelial carcinomas were significantly higher than those in the normal mucosa. In contrast, MT3-MMP mRNA was little expressed in both tissues, and the amount of MT3-MMP mRNA appeared to be much lower than MT1-MMP and MT2-MMP in the tissue samples. In terms of the tumor multiplicity, MT1-MMP and MT2-MMP mRNA expressions in the group of multiple tumors were significantly higher than those in the solitary tumor group. The carcinoma cells were immunostained for MT1-MMP predominantly in invasive and superficial carcinoma cells. The immunoreactivity was more intense in the invasive type than in the superficial type. Conclusions: It is suggested that MT1-MMP and MT2-MMP play an important role in the development of human urothelial carcinomas and reflect some aspects of the pathogenesis of multifocal occurrence. In spite of the possible contribution to the invasive and metastatic phenotype, MT1-MMP mRNA and its product are thought to be expressed already in the clinical superficial stage in some cases of this tumor type. References 1 : Metalloproteinases and their inhibitors in matrix remodeling. Trends Genet.1990; 6: 121. Google Scholar 2 : Biology and biochemistry of proteinases in tumor invasion. Physiol. Rev.1993; 73: 161. Google Scholar 3 : Tumor cell interactions with the extracellular matrix during invasion and metastasis. Ann. Rev. Cell Biol.1993; 9: 541. Google Scholar 4 : Cell-mediated degradation of type collagen and gelatin films is dependent on the activation of matrix metalloproteinase. Biochem. 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Volume 160Issue 4October 1998Page: 1540-1545 Advertisement Copyright & Permissions© 1998 by American Urological Association, Inc.MetricsAuthor Information YASHUHIDE KITAGAWA More articles by this author KAZUTO KUNIMI Requests for reprints: Department of Urology, Kanazawa University School of Medicine, Takara-machi, 13-1, Kanazawa, 920 Japan. More articles by this author HIDEAKI ITO More articles by this author HIROSHI SATO More articles by this author TADAO UCHIBAYASHI More articles by this author YASUNORI OKADA More articles by this author MOTOHARU SEIKI More articles by this author MIKIO NAMIKI More articles by this author Expand All Advertisement PDF downloadLoading ...