ENHANCED INHIBITORY EFFECT OF POLYMERIC STAR BURST FORMED YIGSR PEPTIDE ON NEWLY ESTABLISHED NUDE-MOUSE SPONTANEOUS ADENOCARCINOMA METASTATIC MODEL

A highly metastatic nude mouse adenocarcinoma cell line, XK-4, was established, and the inhibitory effect of the polymeric star burst YIGSR peptide on XK-4 metastasis was examined. XK-4 adenocarcinoma arose spontaneously in a nude mouse after the subucutaneous transplantation of a human colon cancer. XK-4 cells were first cultured in February, 1990 after serial transplantation of the tumor in nude mice since October, 1985. The XK-4 cell line produces blood borne lung or liver metastasis 2 weeks after injection into the tail vein or anterior mesenteric vein, respectively. Chromosomal analysis of the XK-4 cell line revealed only murine chromosomes, and isozyme analysis showed a murine pattern. Transplantation of XK-4 cells into a thymus-intact litter mate was rejected. These results suggest that the XK-4 adenocarcinoma grew spontaneously in the nude mouse due to some kind of human cancer stimulation. A peptide consisting of the active domain of laminin, YIGSR, was chemically synthesized as a polymer with a star burst pattern. The inhibitory effect of polymeric star burst YIGSR on XK-4 metastasis was enhanced, compared with monomeric YIGSR. These effects appear to be due to the prolonged half-life of polymeric star burst YIGSR in vivo, and increased binding of polymeric star burst YIGSR to the YIGSR receptor. In this study we established a new metastatic model, and confirmed the enhanced metastatic inhibitory effect of a polymeric form of the star burst YIGSR peptide.