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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >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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Antitumor activity of mannan-binding protein in vivo as revealed by a virus expression system: Mannan-binding protein- dependent cell-mediated cytotoxicity

机译：病毒表达系统揭示了甘露聚糖结合蛋白在体内的抗肿瘤活性：甘露聚糖结合蛋白依赖性细胞介导的细胞毒性

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摘要

Mannan-hinding protein (MBP), a Ca~2+- dependent mammalian lectin specific for mannose and N- acetylglucosamine, is an important serum component asso- ciated with innate immunity. MBP activates complement and functions as a direct opsonin on binding to mannooligosac- charide-bearing pathogens. We have found that MBP recog- nizes and binds specifically to oligosaccharide ligands ex- pressed 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 intra- tumoral 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-mediatcd cytotoxici- ty(MDCC). In addition, this study provides a model for the development of an effective and specific host defense factor for cancer gene therapy.
机译：甘露聚糖蛋白（MBP）是一种对甘露糖和N-乙酰氨基葡萄糖具有特异性的Ca〜2 +依赖性哺乳动物凝集素，是与先天免疫相关的重要血清成分。 MBP激活补体，并在与含甘露寡糖的病原体结合时充当直接调理素。我们发现MBP可以识别并与人结肠直肠癌表面表达的寡糖配体特异性结合。有趣的是，当通过肿瘤内或皮下注射给药时，证实了携带人MBP基因的重组牛痘病毒对移植于KSN裸鼠中的人结肠直肠癌细胞具有有效的生长抑制活性。此外，该治疗导致荷瘤小鼠的寿命显着延长。该作用似乎是MBP局部产生的结果。出乎意料的是，突变体MBP基本没有补体激活活性，其活性几乎与野生型MBP一样。这些结果表明MBP具有以前未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，这项研究为癌症基因治疗的有效和特异性宿主防御因子的发展提供了模型。

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