Antitumor activity of mannan-binding protein in vivo as revealed by a virus expression system: mannan-binding proteindependent cell-mediated cytotoxicity.
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.
Ma
Y
Y
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.
Uemura
K
K
Oka
S
S
Kozutsumi
Y
Y
Kawasaki
N
N
Kawasaki
T
T
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*
D000970:Antineoplastic Agents; D002352:Carrier Proteins; D037222:Collectins