Levels of proteins that naturally inhibit some of these proteases increase during the immune response to tumors. The increased production of these proteins may reflect the host's attempt to suppress tumor cell metastasis. The observation that TIMPs are secreted by tumor cells with low metastatic potential suggests that TIMPs or drugs that act like them may be useful therapeutic agents in the prevention of tumor metastasis. Indeed, transfection of carcinomatous mammary cells with the maspin gene, which encodes a protease inhibitor of the serpin family, reduces the invasive potential of the cells but not their growth rate. Evidence suggests that the growth of a tumor beyond a certain size requires angiogenesis, which may also permit and even facilitate metastasis.
Tumor cells can induce angiogenesis through a variety of soluble factors.
Moreover, the initial phase of angiogenesis, in which endothelial cells exit the primary blood vessel, involves cell migration and degradation of the extracellular matrix by proteases similar to those implicated in metastasis. Thus, angiogenesis by normal endothelial cells and metastasis by tumor cells are functionally similar processes. A detailed comparison of the mechanisms that regulate these two processes may therefore lead to the identification of tumor-specific targets for immunotherapy.