Abstract
Thrombospondin 1 (TSP1) is a large multi-functional extracellular matrix molecule that is a member of a family of glycoproteins. TSP1 is a prominent component of the alpha granule of platelets, and is produced by numerous cell types, including endothelial cells, fibroblasts, macrophages, monocytes, keratinocytes, and some tumor cells (Frazier, 1987; Lawler, 1986). TSP1 has been described to have many physiologic functions, including involvement in cell migration, recognition, and binding. The multi-functional nature of TSP1 is illustrated by the complex molecular structure (Figure 1). TSP1 exists as a trimer of three identical subunits, each with a molecular weight of 180 kd. Each subunit is dumbbell shaped, containing globular NH2- and COOH terminal domains joined by a central stalk (Galvan et al., 1985; Lawler et al., 1985). The NH2- domain has heparin binding activity, while the COOH domain contains a cell attachment region. The stalk can be further divided into four regions: 1) a region containing the cysteines involved in interchain disulfide bonding, 2) a region homologous to procollagen type I, 3) a region with three properdin (Type 1) repeats, and 4) a region with three EGF-like (Type 2) repeats.
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References
Apelgren, L.D., and Bumol, T.F., 1989, Biosynthesis and secretion of thrombospondin in human melanoma cells, Cell Biol. Intl. Rep. 13: 189–195.
Bagavandoss, P., and Wilks, J.W., 1990, Specific inhibition of endothelial cell proliferation by thrombospondin, Biochem. Biophys. Res. Comm. 170: 867–872.
BenEzra, D., Griffin, B.W., Maftzir, G., and Aharonov, O., 1993, Thrombospondin and in vivo angiogenesis induced by basic fibroblast growth factor or lipopolysaccharide, Invest. Ophthamol. Vis. Sci. 34: 3601–3608.
Botney, M.D., Kaiser, L.R., Cooper, J.D., Mecham, R.P., Parghi, D., Roby, J., and Parks, W.C., 1992, Extracellular matrix protein gene expression in atherosclerotic hypertensive pumonary arteries, Am. J. Pathol. 140: 357–364.
Canfield, A.E., Boot-Hadford, P., and Schor, A.M., 1990, Thrombospondin gene expression by endothelial cells in culture is modulated by cell proliferation, cell shape, and the substratum, Biochem. J. 268: 225–230.
Castle, V., Varani, J., Fligiel, S., Prochownik, E., and Dixit, V., 1991, Anti-sense mediated reduction in thrombospondin reverses the malignant phenotype of a human squamous carcinoma, J. Clin. Invest. 87: 1883–1888.
Clezardin, P., Jouishomme, H., Chavassieux, P., and Marie, P.J., 1989, Thrombospondin is synthesized and secreted by human osteoblasts and osteosarcoma cells, Eur. J. Biochem. 181: 721–726.
Dameron, K.M., Volpert, O.V., Tainsky, M.A., and Bouck, N., 1994, Control of angiogenesis in fibroblasts by p53 regulation of thrombospondin-1, Science 265:1582–1584.
DiPietro, L.A. and Polverini, P.J., 1993, Angiogenic macrophages produce the angiogenic inhibitor thrombospondin 1, Am. J. Pathol. 143: 678–684.
DiPietro, L.A., Nebgen, D.R., and Polverini, P. J., 1994, Down-regulation of endothelial cell thrombospondin 1 enhances in vitro angiogenesis, J. Vasc. Res. 31: 178–185.
DiPietro, L.A., Nissen, N.N., Gamelli, R.L., Koch, A.E., and Polverini, P. J., 1995, Inhibition of wound repair by topical antisense thrombospondin 1 oligomers, FASEB J. 9: A696.
Frazier, W. A., 1987, Thrombospondin: a modular adhesive glycoprotein of platelets and nucleated cells, J. Cell Biol. 105:625–32.
Galvan, N.J., Dixit, V.M., O’Rourke, K.M., Santoro, S.A., Grant, G.A., and Frazier, W.A., 1985, Mapping of epitopes for monoclonal antibodies against human platelet thrombospondin with electron microscopy and high sensitivity amino acid sequencing, J. Cell Biol. 101: 1434–1441.
Good, D.J., Polverini, P.J., Rastinejad, F., LeBeau, M.M., Lemons, R.S., Frazier, W.A. and Bouck, N.P., 1990, A tumor suppressor-dependent inhibitor of angiogenesis is immunologically and functionally indistinguishable from a fragment of thrombospondin, Proc. Nat. Acad. Sci. USA. 87: 6624–6628.
Huber, A.R., Ellis, S., Johnson, K.J., Dixit, V.M., and Varani, J., 1992, Monocyte diapedesis through an in vitro vessel wall construct: inhibition with monoclonal antibodies to thrombospondin, J. Leukoc. Biol. 52: 524–528.
Iruela-Arispe, M.L., Bornstein, P., and Sage, H., 1991a, Thrombospondin exerts an antiangiogenic effect on cord formation by endothelial cells in vitro, Proc. Natl. Acad. Sci. USA 88: 5026–5030.
Iruela-Arispe, M.L., Hasselar, P., and Sage, H. 1991b, Lab. Invest. 64: 174–186.
Jaffe, E.A., Ruggiero, J.T., and Falcone, D.J., 1985, Monocytes and macrophages synthesize and secrete thrombospondin, Blood 65: 79–84.
Kane, C.J.M., Hebda, P.A., Mansbridge, J.N., and Hanawalt, P.C., 1991, Direct evidence for spatial and temporal regulation of transforming growth factor β1 expression during cutaneous wound healing, J. Cell. Physiol. 148: 157–173.
Koch, A.E., Friedman, J., Burrows, J.C., Haines, G.K., and Bouck, N.P., 1993, Localization of the angiogenesis inhibitor thrombospondin in human synovial tissues, Pathobiology 61: 1–6.
Lahav, J., 1988, Thrombospondin inhibits adhesion of endothelial cells, Exp. Cell Res. 177: 199–204.
Lawler, J., Derick, L.H., Connolly, J.E., Chen, J.H., and Chao, F.C., 1985, The structure of human platelet thrombospondin, J. Biol. Chem. 260: 3672–3772.
Lawler, J., 1986, The structural and functional properties of thrombospondin, Blood 67: 1197–1209.
Mansfield, P. J., and Suchard, S.J., 1994, Thrombospondin promotes Chemotaxis and haptotaxis of human peripheral monocytes, J. Immunol. 153: 4219–4229.
McPherson, J.H., Sage, H., and Bornstein, P., 1981, Isolation and characterization of a glycoprotein secreted by aortic endothelial cells in culture: apparent identity with platelet thrombospondin, J. Biol. Chem. 256:11330–11336.
Murphy-Ullrich, J.E., and Höök, M., 1989, Thrombospondin modulates focal adhesions in endothelial cells, J. Cell Biol. 109: 1309–1319.
Mustoe, T.A., Pierce, G.F., Thomason, A., Gramates, P., Sporn, M.B., and Deuel, T.F., 1987, Accelerated healing of incisional wounds by transforming growth factor-β, Science 236: 1333–1336.
Nickoloff, B.J., Mitra, R.S., Varani, J., Dixit, V.M., and Polverini, P.J., 1994, Aberrant production of interleukin-8 and thrombospondin-1 by psoriatic keratinocytes mediates angiogenesis, Am. J. Pathol. 144: 820–828.
Nicosia, R.F., and Tuszynyski, G.P., 1994, Matrix-bound thrombospondin promotes angiogenesis in vitro, J. Cell Biol. 124: 183–193.
Ostergaard E., and Flodgaard, H., 1992, A neutrophil-derived proteolytic inactive elastase homologue (hHBP) mediates reversible contraction of fibroblasts and endothelial cell monolayers and stimulates monocyte survival and thrombospondin secretion, J. Leukoc. Biol. 51: 316–323.
Polverini, P.J., DiPietro, L.A., Dixit, V.M., Hynes, R.O., and Lawler, J., 1995, Thrombospondin 1 knockout mice show delayed organization and prolonged neovascularization of skin wounds, FASEB J. 9: A212.
Pratt, D.A., Miller, W.R., and Dawes, J., 1989, Thrombospondin in malignant and non-malignant breast tissue, Eur. J. Cancer Clin. Oncol. 25: 343–350.
Rastinejad, F., Polverini, P. J., and Bouck, N.P., 1989, Regulation of the activity of a new inhibitor of angiogenesis by a cancer suppressor gene, Cell 56: 345–355.
Reed, M.J., Puolakkainen, P., Lane, T.F., Dickerson, D., Bornstein, P., and Sage, E.H., 1993, Differential expression of SPARC and thrombospondin 1 in wound repair: immunolocalization and in situ hybridization, J. Histochem. Cytochem. 41: 1467–1477.
Roberts, A.B., Sporn, M.B., Assoian, R.K., Smith, J.M., Roche, N.S., Wakefield, L.M., Heine, U.I., Liotta, L.A., Falanga, V., Kehrl, J.H., et al., 1986, Transforming growth factor type beta: rapid induction of fibrosis and angiogenesis in vivo and stimulation of collagen formation in vitro, Proc. Natl. Acad. Sci. USA. 83:4167–4171.
Schultz-Cherry, S. and Murphy-Ullrich, J.E., 1993, Thrombospondin causes activation of latent transforming growth factor-β secreted by endothelial cells by a novel mechanism, J. Cell. Biol. 122: 923–932.
Taraboletti, G., Belotti, D., and Giavazz, R., 1992, Thrombospondin modulates basic fibroblast growth factor activities on endothelial cells, EXS 61: 210–213.
Tolsma, S.S., Volpert, O.V., Good, D.J., Frazier, W.A., Polverini, P.J., and Bouck, N., 1993, Peptides derived from two separate domains of the matrix protein thrombospondin 1 have anti-angiogenic activity, J. Cell Biol. 122:497–511.
Tuszynski, G.P., Gasic, T.B., Rothman, V.L., Knudsen, K.A., and Gasic, G.J., 1987, Thrombospondin, a potentiator of tumor cell metastasis, Cancer Res. 47: 4130–4133.
Varani, J., Carey, T.E., Fligiel, S.E.G., McKeever, P.E., and Dixit, V.M., 1987, Tumor type-specific differences in cell-substrate adhesion among human tumor cell lines, Int. J. Cancer 39: 397–403.
Varani J., Stoolman, L., Wang, T., Schuger, L., Flippen, C, Dame, M., Johnson, K.J., Todd, R.F., Ryan, U.S., and Ward, P.A., 1991, Thrombospondin production and thrombospondin-mediated adhesion in U937 cells, Exp. Cell Res. 195: 177–182.
Weinstat-Saslow, D.L., Zabrenetzky, V.S., VanHoutte, K., Frazier, W.A., Roberts, D.D., and Steeg, P.S., 1994, Transfection of thrombospondin 1 complementary DNA into human breast carcinoma cell line reduces primary tumor growth, metastatic potential, and angiogenesis, Cancer Res. 54: 6504–6511.
Zabrenetzsky, V., Harris, C.C., Steeg, P., and Roberts, D.D., 1994, Expression of the extracellular matrix molecule thrombospondin inversely correlates with malignant progression in melanoma, lung, and breast carcinoma cell lines, Int. J. Cancer 59: 191–195.
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© 1996 Plenum Press, New York
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DiPietro, L.A., Polverini, P.J. (1996). The Role of Thrombospondin in Angiogenesis. In: Maragoudakis, M.E. (eds) Molecular, Cellular, and Clinical Aspects of Angiogenesis. NATO ASI Series, vol 285. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-0389-3_10
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DOI: https://doi.org/10.1007/978-1-4613-0389-3_10
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