Clinical data has shown a positive correlation between the frequency of TAMs and the density of microvessels.90 Macrophage depletion by zoledronic acid or clodronate-encapsulated liposomes, in combination with sorafenib, further reduced tumor growth, lung metastasis, and tumor angiogenesis.88 Moreover, VEGF may be released from the ECM via MMP-9 (which was produced by TAM)-mediated proteolysis,91 thus providing an alternative, but still VEGF-dependent route for promoting angiogenesis. This evidence concerns the gene MMP9 and neoplasm.