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SPARC and the Extracellular Matrix: Implications for Cancer and Wound Repair

  • Chapter
Attempts to Understand Metastasis Formation I

Part of the book series: Current Topics in Microbiology 213/I and Immunology ((CT MICROBIOLOGY,volume 213/1))

Abstract

Complex interactions between cells and the extracellular matrix are requisite during development, wound repair, and neoplasia. Proteins that regulate cell-cell and cell-matrix contacts are likely to influence both normal responses (e.g. wound healing) and abnormal processes (e.g. malignant transformation). The glycoprotein SPARC (secreted protein, acidic and rich in cysteine), also termed osteonectin, BM-40, and 43 K protein, has been classified, along with tenascin and thrombospondin, as an “anti-adhesinan ” (for review see Sage and Bornstein 1991). For many cell types, this function promotes cell rounding, a decrease in focal adhesions, and diminished cell-cell and cell-surface contacts. The at¬tendant consequences for tissue remodeling and cellular migration implicate SPARC as a regulatory protein in both wound healing and cancer. The purpose of this chapter is to review the properties of this protein and the functional implications for SPARC in neoplasia and tissue repair.

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References

  • Bagavandoss P, Wilks JW (1990) Specific inhibition of endothelial cell proliferation by throm-bospondin. Biochem Biophys Res Commun 170: 867–872.

    Article  PubMed  CAS  Google Scholar 

  • Bellahcéne A, Castronovo V (1995) Increased expression of osteonectin and osteopontin, two bone matrix proteins, in human breast cancer. Am J Pathol 146: 95–100.

    PubMed  Google Scholar 

  • Clezardin P, Malaval L, Ehrensperger A, Delmas PD, Dechavanne M, McGregor JL (1988) Complex formation of human thrombospondin with osteonectin. Eur J Biochem 175: 275–84.

    Article  PubMed  CAS  Google Scholar 

  • Duffy MJ (1992) The role of proteolytic enzymes in cancer invasion and metastasis. Clin Exp Metastasis 10: 145–155.

    Article  PubMed  CAS  Google Scholar 

  • Engel J, Taylor W, Paulsson M, Sage EH, Hogan B (1987) Calcium binding domains and calcium-induced conformational transition of SPARC/BM-40/osteonectin, an extracellular glycoprotein expressed in mineralized and nonmineralized tissues. Biochemistry 26: 6958–6965.

    Article  PubMed  CAS  Google Scholar 

  • Everitt E, Sage EH (1992) Expression of SPARC is correlated with altered morphologies in transfected F9 embryonal carcinoma cells. Exp Cell Res 199: 134–146.

    Article  PubMed  CAS  Google Scholar 

  • Falanga V, Zitelli JA, Eaglstein WH (1988) Wound healing. J Am Acad Dermatol 19: 559–563.

    Article  PubMed  CAS  Google Scholar 

  • Funk SE, Sage EH (1991) The Ca2+-binding glycoprotein SPARC modulates cell cycle progression in bovine aortic endothelial cells. Proc Natl Acad Sci USA 88: 2648–2652.

    Article  PubMed  CAS  Google Scholar 

  • Funk SE, Sage EH (1993) Differential effects of SPARC and cationic SPARC peptides on DNA synthesis by endothelial cells and fibroblasts. J Cell Physiol 154:53–63.

    Article  PubMed  CAS  Google Scholar 

  • Goldblum SE, Ding X, Funk SE, Sage EH (1994) SPARC (secreted protein acidic and rich in cysteine) regulates endothelial cell shape and barrier function. Proc Natl Acad Sci USA 91: 3448–3452.

    Article  PubMed  CAS  Google Scholar 

  • Good DJ, Polverini PJ, Rastinejad F, LeBeau MM, Lemons RS, Frazier WA, Bouck NP (1990) A tumor suppressor-dependent inhibitor of angiogenesis is immunologically and functionally indistingui¬shable from a fragment of thrombospondin. Proc Natl Acad Sci USA 87: 6624–6628.

    Article  PubMed  CAS  Google Scholar 

  • Hasselaar P, Sage EH (1992) SPARC antagonizes the effect of basic fibroblast growth factor on the migration of bovine aortic endothelial cells. J Cell Biochem 49: 272–283.

    Article  PubMed  CAS  Google Scholar 

  • Hasselaar P, Loskutoff DJ, Sawdey M, Sage EH (1991) SPARC induces the expression of type I plasminogen activator inhibitor in cultured bovine aortic endothelial cells. J Biol Chem 266: 13178–13184.

    PubMed  CAS  Google Scholar 

  • Holland PWH, Harper SJ, McVey JH, Hogan BLM (1987) In vivo expression of mRNA for the Ca++binding protein SPARC (osteonectin) revealed by in situ hybridization. J Cell Biol 105: 473–482.

    Article  PubMed  CAS  Google Scholar 

  • Iruela-Arispe ML, Hasselaar P, Sage EH (1991a) Differential expression of extracellular proteins is correlated with angiogenesis in vitro. Lab Invest 64: 174–186.

    PubMed  CAS  Google Scholar 

  • Iruela-Arispe ML, Bornstein P, Sage EH (1991b) Thrombospondin exerts an antiangiogenic effect on cord formation by endothelial cells in vitro. Proc Natl Acad Sci USA 88: 5026–5030.

    Article  PubMed  CAS  Google Scholar 

  • Iruela-Arispe ML, Lane TF, Redmond D, Reilly M, Bolender RP, Kavanagh TJ, Sage EH (1995) Expression of SPARC during development of the chicken chorioallantoic membrane: evidence for regulated proteolysis in vivo. Mol Biol Cell 6: 327–343.

    PubMed  CAS  Google Scholar 

  • Kasugai S, Todescan R, Nagata T, Yao K-L, Butler WT, Sodek J (1991) Expression of bone matrix proteins associated with mineralized tissue formation by adult rat bone marrow cells in vitro: inductive effects of dexamethasone on the osteoblastic phenotype. J Cell Physiol 147: 111–120.

    Article  PubMed  CAS  Google Scholar 

  • Lane TF, Sage EH (1990) Functional mapping of SPARC: peptides from two distinct Ca++-binding sites modulate cell shape. J Cell Biol 111: 3065–3076.

    Article  PubMed  CAS  Google Scholar 

  • Lane TF, Sage EH (1994) The biology of SPARC, a protein that modulates cell-matrix interactions. FASEB J 8: 163–173.

    PubMed  CAS  Google Scholar 

  • Lane TF, Iruela-Arispe ML, Sage EH (1992) Regulation of gene expression by SPARC during angiogenesis in vitro: changes in fibronectin, thrombospondin-1, and plasminogen activator inhibitor-1. J Biol Chem 267: 16736–16745.

    PubMed  CAS  Google Scholar 

  • Lane TF, Iruela-Arispe ML, Johnson RS, Sage EH (1994) SPARC is a source of copper-binding peptides that stimulate angiogenesis. J Cell Biol 4: 929–943.

    Article  Google Scholar 

  • Mann K, Deutzmann R, Paulsson M, Timpl R (1987) Solubilization of protein BM-40 from a basement membrane tumor with chelating agents and evidence for its identity with steonectin and SPARC. FASEB J 218: 167–172.

    CAS  Google Scholar 

  • Maquart F-X, Bellon G, Chaqour B, Wegrowski J, Patt LM, Trachy RE, Monboisse JC, Chastang F, Birembaut P, Gillery P, Borei JP (1993) In vivo stimulation of connective tissue ccumulation by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+ in rat experimental wounds. J Clin Invest 92: 2368–2376.

    Article  PubMed  CAS  Google Scholar 

  • Masaki N, Rodan GA (1989) Type β transforming growth factor regulates expression of genes encoding bone matrix proteins. Connect Tissue Res 21: 71–75.

    Article  Google Scholar 

  • Mason IJ, Murphy D, Munke M, Francke U, Elliott RW, Hogan BLM (1986a) Developmental and transformation-sensitive expression of the SPARC gene on mouse chromosome 11. EMBO J 5: 1831–1837.

    PubMed  CAS  Google Scholar 

  • Mason IJ, Taylor A, William JG, Sage EH, Hogan BLM (1986b) Evidence from molecular cloning that SPARC, a major product of mouse embryo parietal endoderm, is related to an endothelial cell “culture shock” glycoprotein. EMBO J 5: 1465–1472.

    PubMed  CAS  Google Scholar 

  • McVey JH, Nomura S, Kelly P, Mason IJ, Hogan BLM (1988) Characterization of the mouse SPARC/osteonectin gene: intron/exon organization and an unusual promoter region. J Biol Chem 263: 11111–11116.

    PubMed  CAS  Google Scholar 

  • Murphy-Ullrich JE, Lane TF, Pallero MA, Sage EH (1995) SPARC mediates focal adhesion disas¬sembly in endothelial cells through a follistatin-like region and the Ca2+-binding EF-hand. J Cell Biochem 57: 341–350.

    Article  PubMed  CAS  Google Scholar 

  • Mustoe TA, Pierce GF, Thomason A, Gramates P, Sporn MB, Deuel TF (1987) Accelerated healing of incisional wounds in rats induced by transforming growth factor β. Science 237: 1333–1335.

    Article  PubMed  CAS  Google Scholar 

  • Neri M, Descalzi-Cancedda F, Cancedda R (1992) Heat-shock response in cultured chick embryo chondrocytes: osteonectin is a secreted heat-shock protein. Eur J Biochem 205: 569–574.

    Article  PubMed  CAS  Google Scholar 

  • Nomura S, Hashmi S, McVey JH, Ham J, Parker M, Hogan BLM (1989) Evidence for positive and negative regulatory elements in the 5’-flanking sequence of the mouse SPARC (osteonectin) gene. J Biol Chem 264: 12201–12207.

    PubMed  CAS  Google Scholar 

  • Otsuka K, Yao KL, Wasi S, Tung PS, Aubin JE, Sodek J, Termine JD (1984) Biosynthesis of osteonectin by fetal porcine calvarial cells in vitro. J Biol Chem 259: 9805–9812.

    PubMed  CAS  Google Scholar 

  • Penttinen RP, Kobayashi S, Bornstein P (1988) Transforming growth factor β increases mRNA for matrix proteins both in the presence and in the absence of changes in mRNA stability. Proc Natl Acad Sci USA 85: 1105–1108.

    Article  PubMed  CAS  Google Scholar 

  • Pickart L (1981) The use of glycyl-histidyl-lysine in culture systems. In Vitro Cell Dev Biol 17: 459–466.

    Article  CAS  Google Scholar 

  • Poole TJ, Zetter BR (1983) Stimulation of rat peritoneal mast cell migration by tumor-derived peptides. Cancer Res 43: 5857–5861.

    PubMed  CAS  Google Scholar 

  • Porter PL, Sage EH, Lane TF, Funk SE, Gown AM (1995) Distribution of SPARC in normal and neoplastic human tissue. J Histochem Cytochem 43: 791–800.

    Article  PubMed  CAS  Google Scholar 

  • Purcell L, Gruia-Gray J, Scanga S, Ringuette M (1993) Developmental anomalies of Xenopus embryos following microinjection of SPARC antibodies. J Exp Zool 265: 153–164.

    Article  PubMed  CAS  Google Scholar 

  • Puolakkainen P, Reed MJ, Gombotz WR, Twardzik DR, Abrass IB, Sage EH (1995) Acceleration of wound healing in aged rats by topical application of transforming growth factor beta 1. Wound Repair Regen 3: 330–339.

    Article  PubMed  CAS  Google Scholar 

  • Raines EW, Lane TF, Iruela-Arispe ML, Ross R, Sage EH (1992) The extracellular glycoprotein SPARC interacts with platelet-derived growth factor (PDGF)-AB and -BB and inhibits the binding of PDGF to its receptors. Proc Natl Acad Sci USA 89: 1281–1285.

    Article  PubMed  CAS  Google Scholar 

  • Raju KS, Alessandri J, Ziehe M, Gullino PM (1982) Ceruloplasmin, copper ions and angiogenesis. J Natl Cancer Inst 69: 1183–1188.

    PubMed  CAS  Google Scholar 

  • Rastinejad R, Polverini PJ, Bouck NP (1989) Regulation of the activity of a new inhibitor of angiogenesis by a cancer suppressor gene. Cell 56: 345–355.

    Article  PubMed  CAS  Google Scholar 

  • Reed MJ, Puolakkainen P, Lane TF, Dickerson D, Bornstein P, Sage EH (1993) Differential expression of SPARC and thrombospondin 1 in wound repair: immunolocalization and in situ hybridization. J Histochem Cytochem 41: 1467–1477.

    Article  PubMed  CAS  Google Scholar 

  • Reed MJ, Vernon RB, Abrass IB, Sage EH (1994) TGF-β1 induces the expression of type I collagen and SPARC, and enhances contraction of collagen gels, by fibroblasts from young and aged donors. J Cell Physiol 158: 169–179.

    Article  PubMed  CAS  Google Scholar 

  • Reed MJ, Johnson RS, Sage EH. Degradation of SPARC by stromelysin and wound fluid: Evidence for regulation of angiogenesis in vivo (manuscript in preparation) Sage EH (1991) Secretion of SPARC by endothelial cells transformed by polyoma middle Toncogene inhibits the growth of normal endothelial cells in vitro. Biochem Cell Biol 70: 579–592.

    Google Scholar 

  • Sage EH, Bornstein P (1991) Extracellular proteins that modulate cell-matrix interactions. J Biol Chem 266:14831–14834.

    PubMed  CAS  Google Scholar 

  • Sage EH, Johnson C, Bornstein P (1984) Characterization of a novel serum albumin-binding glycoprotein secreted by endothelial cells in culture. J Biol Chem 259: 3993–4007.

    PubMed  CAS  Google Scholar 

  • Sage EH, Tupper J, Bramson R (1986) Endothelial cell injury in vitro is associated with increased secretion of an Mr 43,000 glycoprotein ligand. J Cell Physiol 127: 373–387.

    Article  PubMed  CAS  Google Scholar 

  • Sage EH, Decker J, Funk SE, Chow M (1989a) SPARC, a Ca2+-binding extracellular protein associated with endothelial cell injury and proliferation. J Mol Cell Cardiol 21: 13–22.

    Article  PubMed  CAS  Google Scholar 

  • Sage EH, Vernon RB, Decker J, Funk S, Iruela-Arispe ML (1989b) Distribution of the calcium-binding protein SPARC in tissues of embryonic and adult mice. J Histochem Cytochem 37: 819–829.

    Article  PubMed  CAS  Google Scholar 

  • Sage EH, Vernon RB, Funk SE, Everitt EA, Angello J (1989c) SPARC, a secreted protein associated with cellular proliferation, inhibits cell spreading in vitro and exhibits Ca+2-dependent binding to the extracellular matrix. J Cell Biol 109: 341–356.

    Article  PubMed  CAS  Google Scholar 

  • Sage EH, Bassuk JA, Yost JC, Folkman JM, Lane TF (1995) Inhibition of endothelial cell proliferation by SPARC is mediated through a Ca2+-binding EF-hand sequence. J Cell Biochem 57: 127–140.

    Article  PubMed  CAS  Google Scholar 

  • Salonen J, Domenicucci C, Goldberg HA, Sodek J (1990) Immunohistochemical localization of SPARC (osteonectin) and denatured collagen and their relationship to remodelling in rat dental tissues. Arch Oral Biol 35: 337–346.

    Article  PubMed  CAS  Google Scholar 

  • Schwarzbauer J, Spencer CS (1993) The Caenorhabditis elegans homolog of the extracellular calcium binding protein SPARC/osteonectin affects nematode body morphology and mobility.Mol Biol Cell 4: 941–952.

    PubMed  CAS  Google Scholar 

  • Stenner DD, Tracy RP, Riggs BL, Mann KG (1986) Human platelets contain and secrete osteonectin, a major protein of mineralized bone. Proc Natl Acad Sci USA 83: 6892–6896.

    Article  PubMed  CAS  Google Scholar 

  • Termine JD, Kleinman HK, Whitson SW, Conn KM, McGarvery ML, Martin GR (1981) Osteonectin, a bone-specific protein linking mineral to collagen. Cell 26: 99–105.

    Article  PubMed  CAS  Google Scholar 

  • Tremble PM, Lane TF, Sage EH, Werb Z (1993) SPARC, a secreted protein associated with morphogenesis and tissue remodeling, induces expression of metalloproteinases in fibroblasts through a novel extracellular matrix-dependent pathway. J Cell Biol 121: 1433–1444.

    Article  PubMed  CAS  Google Scholar 

  • Tyree B (1989) The partial degradation of osteonectin by a bone-derived metalloprotease enhances binding to type I collagen. J Bone Miner Res 4: 877–883.

    Article  PubMed  CAS  Google Scholar 

  • Villarreal XC, Mann KG, Long GL (1989) Structure of human osteonectin based upon analysis of cDNA and genomic sequences. Biochemistry 28: 6483–6491.

    Article  PubMed  CAS  Google Scholar 

  • Villarreal XC, Grant BW, Long GL (1991) Demonstration of osteonectin mRNA in megakaryocytes: the use of the polymerase chain reaction. Blood 78: 1216–1222.

    PubMed  CAS  Google Scholar 

  • Vuorio T, Kähäri V-M, Black C, Vuorio E (1991) Expression of osteonectin, decorin, and transforming growth factor-β1 genes in fibroblast cultures from patients with systemic sclerosis and morphea. J Rheumatol 18: 247–251.

    PubMed  CAS  Google Scholar 

  • Wewer U, Albrechtsen R, Fisher L, Young M, Termine J (1988) Osteonectin/SPARC/BM-40 in human decidua and carcinoma, tissues characterized by de novo formation of basement membrane. Am J Pathol 132: 345–355.

    PubMed  CAS  Google Scholar 

  • Wrana JL, Overall CM, Sodek J (1991) Regulation of the expression of a secreted acidic protein rich in cysteine (SPARC) in human fibroblasts by transforming growth factor β. Eur J Biochem 197: 519–528.

    Article  PubMed  CAS  Google Scholar 

  • Yost JC, Sage EH (1993) Specific interaction of SPARC with endothelial cells is mediated through a carboxyl-terminal sequence containing a calcium-binding EF hand. J Biol Chem 268: 25790–25796.

    PubMed  CAS  Google Scholar 

  • Zetter BR, Rasmussen N, Brown L (1985) Methods in laboratory investigation. An in vivo assay for chemoattractant activity. Lab Invest 53: 362–368.

    CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Medicine, University of Washington, Box 359755, Seattle, WA, 98195, USA

    M. J. Reed

  2. Department of Biological Structure, University of Washington, Box 357420, Seattle, WA, 98195, USA

    E. H. Sage

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  1. M. J. Reed
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  2. E. H. Sage
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Editors and Affiliations

  1. Basel Institute for Immunology, Grenzacherstraße 487, CH-4005, Basel, Switzerland

    Ursula Günthert Ph.D., P.D.

  2. Max-βDelbrūck-Centrum für Molekulare Medizin, Robert-Rōssle-Straße 10, D-13122, Berlin, Germany

    Walter Birchmeier Ph.D.

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© 1996 Springer-Verlag Berlin Heidelberg

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Reed, M.J., Sage, E.H. (1996). SPARC and the Extracellular Matrix: Implications for Cancer and Wound Repair. In: Günthert, U., Birchmeier, W. (eds) Attempts to Understand Metastasis Formation I. Current Topics in Microbiology 213/I and Immunology, vol 213/1. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-61107-0_6

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  • DOI: https://doi.org/10.1007/978-3-642-61107-0_6

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