Establishment of orthotopic mouse model of human renal cell carcinoma and expression analysis of metastasis-associated genes / 第二军医大学学报

ABSTRACT

Objective: To establish orthotopic mouse models of human renal cell carcinoma and to separate metastatic or non-metastatic renal cell carcinoma (RCC) from the same source. Methods: Surgical specimens/cell suspensions were transplanted into the various tissues of BALB/c nude mice (subcutis, cellular orthotopic injection into renal capsule, perinephrium, surgical orthotopic implantation into renal capsule). Tumorigenicity and metastasis were subsequently evaluated. Immunohistochemical analysis was employed to determine the expression of VEGF, bFGF, P16, Bcl-2 and C-met in the metastatic and non-metastatic RCC xenograft. Results: The incidences of tumorigenicity and metastasis of orthotopic model were the highest, being at 73.3% (11/15) and 20% (3/15), respectively. Compared with the non-metastastic RCC, VEGF expression was upregulated in the metastatic RCC (P<0.05), while the expression of C-met was downregulated significantly (P<0.05); the expression of bFGF, Bcl-2 and P16 was also downregulated but without significance. Conclusion: Mouse orthotopic transplantation is the most effective way for the growth and natural metastasis of human RCC. Primary and metastatic RCC from the same patient has been successfully harvested. Expression of VEGF in the metastatic tumor tissues is significantly higher than that in the non-metastatic RCC.