Studies of ccRCC cell lines with or without the expression of wild-type VHL indicate that VHL suppresses the expression of matrix metallopeptidase (MMP) 2 and 9, while amplifying the expression of tissue inhibitor of metalloproteinase (TIMP) 1 and 2 [51], and that the level of MMP2 expression in ccRCC cells correlates with their capacity for invasion in three-dimensional cell culture [48]. This evidence concerns the gene MMP2 and nonpapillary renal cell carcinoma.