Browsing by Author "Polverini, Peter J."

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    Peptides Derived from Two Separate Domains of the Matrix Protein Thrombospondin-1 Have Anti-Angiogenlc Activity
    Tolsma, Sara S.; Volpert, Olga V.; Good, Deborah J.; Frazier, William A.; Polverini, Peter J.; Bouck, Noel (Rockefeller University Press, 1993-07-01)
    Thrombospondin-1 (TSP1) is a large modular matrix protein containing three identical disulfide-linked 180-kD chains that inhibits neovascularization in vivo (Good et al., 1990). To determine which of the structural motifs present in the 180-kD TSP1 polypeptide mediate the anti-angiogenic activity, a series of protease-generated fragments were tested using several in vitro and in vivo assays that reflect angiogenic activity. The majority of the anti-angiogenic activity of TSP1 resides in the central 70-kD stalk region which alone could block neovascularization induced by bFGF in the rat cornea in vivo and inhibit both migration in a modified Boyden chamber and [~H]thymidine incorporation stimulated by bFGF in cultured capillary endothelial cells. Although TSP1 has been shown to bind active TGF/31, this cytokine could not account for the inhibitory effects of the stalk region of TSP1 on cultured endothelial cells.
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    A Tumor Suppressor-Dependent Inhibitor of Angiogenesis Is Immunologically and Functionally Indistinguishable From a Fragment of Thrombospondin
    Good, Deborah J.; Polverini, Peter J.; Rastinejad, Farzan; Le Beau, Michelle M.; Lemons, Richard S.; Frazier, William A.; Bouck, Noel P. (National Academy of Sciences, 1990-09)
    A secreted inhibitor of angiogenesis that is controlled by a tumor suppressor gene in hamster cells has been found to be similar to a fragment of the platelet and matrix protein thrombospondin. The two proteins were biochemically similar and immunologically crossreactive and could substitute for one another in two functional assays. Human thrombospondin inhibited neovascularization in vivo and endothelial cell migration in vitro, as does the hamster protein, gp140. gp140 sensitized smooth muscle cells to stimulation by epidermal growth factor, as does human thrombospondin. The thrombospondin gene has been localized on human chromosome 15. These results demonstrate a function for the ubiquitous adhesive glycoprotein thrombospondin that is likely to be important in the normal physiological down-regulation of neovascularization. In addition, they raise the possibility that thrombospondin may be one of a number of target molecules through which a tumor suppressor gene could act to restrain tumor growth.