title: Antitumor activity of mannan-binding protein in vivo as revealed by a virus expression system: mannan-binding proteindependent cell-mediated cytotoxicity.
abstract: Mannan-binding protein (MBP), a Ca2+-dependent mammalian lectin specific for mannose and N-acetylglucosamine, is an important serum component associated with innate immunity. MBP activates complement and functions as a direct opsonin on binding to mannooligosaccharide-bearing pathogens. We have found that MBP recognizes and binds specifically to oligosaccharide ligands expressed on the surfaces of a human colorectal carcinoma. Interestingly, the recombinant vaccinia virus carrying human MBP gene was demonstrated to possess a potent growth-inhibiting activity against human colorectal carcinoma cells transplanted in KSN nude mice when administered by intratumoral or subcutaneous injection. Moreover, a significant prolongation of life span of tumor-bearing mice resulted from the treatment. This effect appears to be a consequence of local production of MBP. Unexpectedly, the mutant MBP, which had essentially no complement-activating activity, was nearly as active as wild-type MBP. These results indicated that MBP has a previously undescribed cytotoxic activity, which we propose to term MBP-dependent cell-mediated cytotoxicity(MDCC). In addition, this study provides a model for the development of an effective and specific host defense factor for cancer gene therapy.
authors.affiliation: Department of Biological Chemistry and Core Research for Evolutional Science and Technology Project, Japan Science and Technology Corporation, Faculty of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Ma
authors.forename: K
authors.initials: K
authors.lastname: Uemura
authors.forename: S
authors.initials: S
authors.lastname: Oka
authors.forename: Y
authors.initials: Y
authors.lastname: Kozutsumi
authors.forename: N
authors.initials: N
authors.lastname: Kawasaki
authors.forename: T
authors.initials: T
authors.lastname: Kawasaki
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002352:Carrier Proteins / Q000235:genetics* / Q000633:toxicity; D002455:Cell Division / Q000235:genetics; D037222:Collectins; D015179:Colorectal Neoplasms / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D015967:Gene Expression Regulation, Viral / Q000235:genetics; D015316:Genetic Therapy; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008819:Mice, Nude; D009154:Mutation; D009374:Neoplasms, Experimental / Q000378:metabolism / Q000401:mortality; D014407:Tumor Cells, Cultured; D014616:Vaccinia virus / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents; D002352:Carrier Proteins; D037222:Collectins