Antitumor activity of mannan-binding proteinin vivoas revealed by a virus expression system: Mannan-binding proteindependent cell-mediated cytotoxicity

Abstract

Mannan-binding protein (MBP), a Ca 2؉ -dependent mammalian lectin specific for mannose and Nacetylglucosamine, 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 growthinhibiting 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.

Mannose‐binding lectin and gastric cancer

“…MBL may perform other, nonmicrobiological, functions during immune competency, 9 and some studies suggest a role in cancer surveillance. 10,11 The influence of MBL status on the risk of acquiring or sustaining H. pylori infection is interesting, and we support Baccarelli et al…”

Cloning of gp-340, a putative opsonin receptor for lung surfactant protein D

“…This effect seems to be a consequence of local production of MBL, and it was anticipated that the killing of the tumor cell was mediated by complement activation and lysis of the tumor cell. Surprisingly, a mutant form of MBL, which had essentially no complement-activating activity, was nearly as active as wildtype MBL, and the results therefore indicate that MBL has a cytotoxic activity on its own (29).…”

“…The finding that gp-340 is an alternative spliced form of the DMBT1 gene raises the possibility that DMBT1 may not be a classical tumor suppressor gene but rather play a role in the interaction of tumor cells and the immune system. Recently, MBL has been shown to recognize and bind specifically to oligosaccharide ligands expressed on the surfaces of a human colorectal carcinoma (29). Recombinant vaccinia virus carrying the human MBL gene was shown to possess a potent growth-inhibiting activity against human colorectal carcinoma cells transplanted in nude mice when administered by intratumoral or subcutaneous injection; a significant prolongation of life span of tumor-bearing mice resulted from the treatment.…”

Mannose-binding lectin and its genetic variants

“…55 Variant recombinant MBL has been shown to retain full potential to kill tumour cells in a cellular-dependent cytotoxicity assay, indicating that some avidity may be retained in the variant molecule. 56 Nevertheless, the biological significance of variant MBL remains to be established.…”