The demonstration that cancers are biologically heterogeneous has a far-reaching implication for therapy. We reviewed recent data from our laboratories that deal with metastatic heterogeneity of human renal cell carcinoma (HRCC) and with the development of nude mouse model for studying HRCC metastasis. The SN12C HRCC line contained heterogeneous subpopulations of cells with different metastatic potential and cells derived from spontaneous lung metastases were in general more metastatic than cells of the SN12C parental line. Nude mice were useful to select such variants with high metastatic potential. Our model for HRCC permits a better understanding of the complexity of the process of tumor evolution, progression and metastasis.

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