Investigation of the angiogenic mechanism at the hepatic metastasis of the colorectal carcinoma.

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Cancer metastasis is completed through complex and multistep processes. We developed an evaluate system of hepatic metastasis in rats by magnetic resonance imaging(MRI)(SIS200 /400) in time course to investigate this complex metstatic processes. We established several highly metastatic cell lines from KM12SM human colorectal carcinoma cell line by in vivo selection. In these highly metastatic celllines, we identified the increased expression of Siaryl Lewis^a and decreased expression of E-cadherin at cell surface by flow-cytometric analysis. These results were reported at some conferences and papors. The tumor cells of RCN-9 rat colon cancer cell line were injected into portal vein of F344 rats. After 4 weeks, the hepatic metastasis was observed and evaluated by using MRI.The hepatic metastasis was identified by T2 weighted images and gadrinium(Gd)-enhancedT1 weighted images, but not by T1 weighted images. The quantitative evaluation of the hepatic metastasis in rats by using MRI seems to be usefull for the study of hepatic tastasis in vivo. Dynamic MRI indicated the kinetics of blood circulation at the tumor. Retinoid has an anti-angiogenic effect. We investigated the anti-metastatic effect of a composite retinoid, TAC101. TAC101 and ATRA inhibited the growth of ECN-9 in vitro. TAC101 inhibited the hepatic metastasis of rat model in vivo, and this phenomenon was observed by MRI in time course.