Effect Of Liver Regeneration On Tumor Recurrence After Liver Transplantation

Objective: To investigate the effect of liver regeneration on tumor recurrence after liver transplantation.Methods: Eighteen healthy adult female Wistar rats were randomly divided into three groups. A suspension of Walker 256 tumor cells in a phosphate buffered solution was prepared at a concentration of 1.0×106 cells/ml before injection. H0 group: The abdominal cavity was entered through a midline incision, and the liver was freed from its ligamentous attachments. The portal vein was injected with 5.0×105 tumor cells; H30 group: Animals that underwent 30% hepatectomy were injected with 5.0×105 tumor cells through the portal vein; H70 group: Animals that underwent 70% hepatectomy were injected with 5.0×105 tumor cells through the portal vein, FK506 was used by subcutaneous injection to mimic the immunosuppression status after liver transplantation. The experiment was terminated on three weeks. The rate of tumor recurrence, change in body weight, tumor-bearing graft weight, tumor-bearing graft to body weight ratio were compared between three groups. The histopathological feature of tumor-bearing livers were evaluated by light microscopy. The level of CAPNS-1 protein expression and the PCNA index were applied to judge the tumor invasiveness. Western Blot, RT-PCR were used respectively to detect the level of c-met, VEGFR-2 protein and m RNA expression, the correlation between the level of c-met、VEGFR-2 and tumor invasiveness was explored.RESULTS: All animals in each experimental group were alive after three weeks and metastatic tumor lesions were found in their lives, so the rate of tumor recurrence was not different between the three experimental groups. However, the animals in group H70 developed larger and more numerous lesions. The change in body weight, tumor-bearing graft weight, tumor-bearing graft to body weight ratio were significantly higher in group H70. The tumors in group H70 showed higher invasiveness and malignant potential. Histological examination with hematoxylin and eosin staining showed tumors in group H70 displayed diffused distribution. The level of CAPNS-1 protein expression and the PCNA index were evaluated in H70. Thelargest resection was also associated with significant up-regulation level of c-met, VEGFR-2 protein and m RNA expression. Furthermore, there was a clear correlation between the level of c-met, VEGFR-2 and the change in body weight, the tumor-bearing graft weight, the tumor-bearing graft to body weight ratio, and the level of CAPNS-1 protein expression.Conclusion: These results suggest that liver regeneration after liver transplantation can facilitate the growth and malignant transformation of tumor, it may attribute to increased growth factors during liver regeneration.