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Cancer is currently one of the most prevalent causes of human deaths in the world.Current therapeutic options aim only to slow the progression of cancer disease.Therefore,a renewed effort must be made to identify relevant endogenous cancer inhibitors that could be exploited as therapeutic drugs.We identified several endogenous anti-cancer molecules,which are released from extracellular matrix (ECM) into the circulating blood of cancer patients.Several of these endogenous circulating molecules were cloned in the laboratory and identified them as inhibitors of angiogenesis and solid tumor growth.These endogenous antiangiogenic proteins binding to cell surface integrins and transduce the signalling mechanisms in regulating antiangiogenic activity.Thus,integrins serve as transmembrane linkers between the ECM and cytoskeleton for outside-in signalling.