Endogenous angioinhibitors from Type IV collagen and their mechanism(s) of action

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M endogenous anti-cancer molecules which are released from extracellular matrix /Type IV collagen were identified as angioinhibitors of tumor growth. These endogenous angioinhibitory molecules bind to the cell surface integrins and transduce the signaling. Thus, cell surface integrins serve as transmembrane linkers between the extracellular matrix and cytoskeleton for outside-in signaling. Four of such endogenous molecules derived from the C-terminal non-collagenous domain of alpha1, 3 and 6 type IV collagen were identified as an inhibitor of angiogenesis, but their mediated angioinhibitory signaling are not known yet. Our findings suggests that these molecules interacting with different cell surface integrins and inhibiting angiogenesis by inhibiting different signaling that leading to inhibition of tumor angiogenesis and tumor growth both in-vitro and in-vivo.