<原著>大腸癌肝転移におけるlaminin結合性レクチンCBP35の関与

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The hematogeneous metastasis to the liver from colorectal cancer is an important factor of patient prognosis. Recently, the carbohydrate-binding protein 35 (CBP35), also known as the macrophage cell surface antigen Mac-2,was identified. CBP35 is a lactosamine-specific lectin whose extracellular properties include the ability to bind to sugar-sites of laminin by a mechanism involving protein-carbohydrate interactions. In this study, CBP expression was examined on 117 primary colorectal cancer and 15 liver metastatic lesions with immunohistochemical staining to clarify the relationship with the liver metastasis. The reaction of staining was classified into three grades ; negative, positive and strongly positive. The strongly positive staining was found in 60% of the primary lesion with liver metastasis, and was significantly higher than that without liver metastasis 18% (P<0.01). In the liver metastatic lesions, the strongly positive CBP35 expression was observed in 73% of the 15 cases. The in vitro adhesion assay demonstrated that the anti-CBP35 antibody and α-lactose effectively inhibited the XK4-A3 and RPMI4788 cell adhesion to laminin. These findings reveal that the expression of CBP35 and the liver metastasis of colorectal cancer may be related with the interaction between CBP35 and laminin. Based on the above hypothesis, the inhibitory effect of CBP35 on the cancer liver metastatic model was examined. The highly metastatic adenocarcinoma cell lines (XK4-A3) and RPMI4788) were infected into the anterior mesenteric vein of nude mouse with various treatments of the anti-CBP35 antibody or lectin-binding sugars, and 2 weeks after the injection, metastatic nodules on the surface of the liver were counted. The average number of metastatic nodules in the control and α-lactose groups were 60±13 (XK4-A3), 75±17 (RPMI14788) and 30±3,45±12 respectively (P<0.001). Metastatic nodules were also significantly reduced with the anti-CBP35 antibody in a dose dependent manner. This CBP35 may thus provide a promising basis for the prevention of cancer metastasis, and the inhibition of CBP35 binding to laminin may prove to be a more effective measure of the inhibition of liver metastasis from colorectal cancer.
近畿大学の論文
1994-12-25

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