Antitumor activity of mannan-binding protein in vivo as revealed by a virus expression system:: Mannan-binding protein-dependent cell-mediated cytotoxicity
Antitumor activity of mannan-binding protein in vivo as revealed by a virus expression system:: Mannan-binding protein-dependent cell-mediated cytotoxicity
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DOI：
10.1073/pnas.96.2.371
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发表时间：
1999-01-19
影响因子：
11.1
通讯作者：
Kawasaki, T
中科院分区：
文献类型：
--
作者：
Ma, Y;Uemura, K;Kawasaki, T
甘露糖结合蛋白（MBP）是一种Ca2+依赖性哺乳动物凝集素，对甘露糖和n-乙酰氨基葡萄糖具有特异性，是与先天免疫相关的重要血清成分。MBP激活补体，并作为直接调理蛋白与甘露寡糖病原体结合。我们已经发现MBP识别并特异性结合在人类结直肠癌表面表达的寡糖配体。有趣的是,携带人MBP基因的重组痘苗病毒通过瘤内或皮下注射，对移植在KSN裸鼠体内的人结直肠癌细胞具有明显的生长抑制活性，并显著延长荷瘤小鼠的寿命。这种效应似乎是局部产生MBP的结果，出乎意料的是，突变型MBP基本上没有补体激活活性，几乎与野生型MBP一样活跃，这些结果表明MBP具有先前描述的细胞毒性活性，我们建议将其称为MBP依赖性细胞介导的细胞毒性（MDCC）。此外，本研究为开发有效的特异性肿瘤基因治疗宿主防御因子提供了模型。
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.