Establishment and characterization of a new human renal cell carcinoma cell line (KG-2) and metastatic model in nude mice

Abstract

A new cultured cell line (KG-2) derived from human renal cell carcinoma and a metastatic model in nude mice were studied. KG-2 was cultured from renal cell carcinoma (clear cell carcinoma) of the left kidney. In vitro doubling time of KG-2 was approximately 50 hours. KG-2 cells produced tumors in both the subcutaneous and renal sub-capsular space in nude mice, with tumorigenicity of 75%, showing no difference between the two sites. Histologically, tumors formed in the subcutaneous sites were hypovascular granular cell carcinoma. Moreover, each tumor was encapsulated by a thick fibrous capsule and never produced distant metastasis or invasion into the surrounding tissue. However, tumors formed in the subrenal capsular space were clear cell carcinoma. These tumors were hypervascular, and produced distant metastases. The most common metastatic site was the lung. Immunohistochemical analysis using anti-human collagenase type IV antibody on tumors formed in subcutaneous and subrenal capsular sites demonstrated that the expression of this enzyme in tumors formed in the subrenal capsular space was much higher than that in tumors formed in the subcutaneous site. Additionally, immunohistochemical study using anti-mouse collagen type IV antibody, a major components of the vascular wall, demonstrated many small densely growing vessels in tumors formed in the subrenal capsular space. In contrast, few vessels were produced in tumors formed in subcutaneous sites. These findings suggest that factors relating to the different injection sites may regulate the production of collagenase type IV secreted by KG-2 cells and neovascularity in nude mice. This metastatic model may be useful in the study of the mechanism of cancer metastases.