TIMP2 and neoplasm: Despite the initial view of the MMP-dependent nature of the antiangiogenic effect of TIMP-2, several studies of mutant Ala+TIMP-2 (lacking MMP-inhibitory activity) have shown that TIMP-2-mediated inhibition of tumor growth occurs, at least in part, independently of MMP inhibition and results from both direct effects of TIMP-2 on tumor cells themselves and modulation of the tumor microenvironment [148].