<原著>Lamininのactive domainであるYIGSRおよびそのsynthetic peptide(polymeric star burst YIGSR)を用いたマウス腺癌肝転移抑制能の検討

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Hematogenous metastasis to the liver from colorectal cancer is an important factor of patient prognosis. An immunohistological study of laminin was made to clarify the relation of laminin and invasion or metastasis of the colorectal cancer. The cancer that stained laminin positive frequently developed into liver metastasis. The binding of the malignant cells with laminin in the basement membranes allows their attachment and activates their invasiveness. Recently, a synthetic peptide (YIGSR) from the B1 chain sequence of laminin was identified as a major site for cell binding. This YIGSR peptide and the polymetric star burst formation YIGSR were synthesized and their inhibitory effect on cancer liver metastasis was examined. A highly metastatic adenocarcinoma cell line (XK-4・Λ-3) was injected into the anterior mesenteric vein of nude mouse with or without admixing with the polypeptide and 2 weeks after the injection, the metastatic nodules on the surface of the liver were counded. The average number of metastatic nodules into control, YIGSR and polymeric star burst YIGSR groups was 113±26,71±9 and 44±19 respectively. While metastatic nodules were significantly reduced in the YIGSR and polymeric star burst YIGSR groups, the inhibition of polymeric star burst YIGSR group was more effective than the original YIGSR group. In vitro adhesion assay demonstrated that the YIGSR was no effect on the XK-4 cell adhesion to the extracelluler matrix. In conclusion the metastatic inhibitory effect was enhanced by the three-dimensional formation of polymeric star burst YIGSR in vivo. This active domain YIGSR of the laminin taken from cell adhesion molecules may thus provide a promising basis for the prevention of cancer metastasis, and this polymeric star burst formation may prove a more effective measure of the inhibition of cancer liver metastasis.
1992-03-25

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