Angiostatin Protein and Other Plasminogen Fragments
In some experimental and clinical presentations ofetastatic disease, a primary tumor can inhibit the growth of its metastases. This phenomenon of the inhibition of tumor growth by tumor mass had been hypothesized to be caused by concomitant immunity (a resistance to second tumor graft in the presence of the first growing tumor) in early publications (1,2). Several other hypotheses have been proposed (reviewed in refs. 3 and 4) but, similarly, had not explained the mechanism of this phenomenon. O’Reilly and Folkman more recently proposed that the phenomenon is the result of the specific inhibition of metastatic growth by the primary tumor. They proposed that a primary tumor initiates its own neovascularization by generating angiogenesis stimulator(s) in excess of angiogenesis inhibitor(s). The positive regulators act most effectively around the primary tumor site, stimulating angiogenesis and primary tumor growth. By virtue of its longer half-life in circulation, negative regulators circulate to other distal sites and inhibit endothelial cell growth, which in turn causes inhibition of metastatic growth (5,6). The hypothesis proposed by O’Reilly and Folkman was validated with the identification of AngiostatinTM protein (AP) generated by the primary tumor, which inhibits angiogenesis and growth in a secondary metastasis (6). Data accumulated to date on the novel protein Angiostatin and another potent endogenous antiangiogenesis inhibitor, EndostatinTM protein, show that, indeed, tumor growth is dependent on angiogenesis (first proposed by Folkman ) and show that the inhibition of angiogenesis can in fact block the growth of metastases, as well as maintain tumors in a dormant state (6,8,9).
KeywordsEndothelial Cell Growth Lewis Lung Carcinoma Primary Tumor Growth Endothelial Cell Surface Metastatic Growth
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