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Gene Review

SPARC  -  secreted protein, acidic, cysteine-rich...

Homo sapiens

Synonyms: BM-40, Basement-membrane protein 40, ON, Osteonectin, Secreted protein acidic and rich in cysteine
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Disease relevance of SPARC

  • Osteonectin/SPARC induction by ectopic beta(3) integrin in human radial growth phase primary melanoma cells [1].
  • Stromal SPARC was linked with tumor necrosis (P = 0.01) and, marginally, with node metastasis (P = 0.07), as well as with high levels of carbonic anhydrase 9 and LDH in cancer cells (P = 0.0001 and P = 0.01, respectively) [2].
  • SPARC produced by melanoma cells modulates polymorphonuclear leukocytes recruitment and anti-tumor cytotoxic activity, indicating a possible role of SPARC in tumor evasion from immune surveillance [3]
  • Using a novel monoclonal antibody (10-255), we examined immunohistochemically the patterns of SPARC expression in non-small cell lung cancer (NSCLC) [2].
  • Immunohistochemical staining for SPARC showed cytoplasmic immunoreactivity of neoplastic cells in all diffuse astrocytomas analyzed [4].
  • SPARC was also coincident with enhanced levels of cancer cell differentiated embryo-chondrocyte expressed gene 1, hypoxia inducible factor 2alpha, and thymidine phosphorylase (P = 0.01, P = 0.05, and P = 0.03, respectively) [2].

High impact information on SPARC

  • The osteonectin-collagen complexes also nucleate mineral phase deposition from metastable balanced salt solutions, Antibodies to osteonectin cross-react with bone and, to a lesser extent, dentin, but not with other tissues [5].
  • Osteonectin is a 32,000 dalton bone-specific protein that binds selectively to both hydroxyapatite and collagen [5].
  • The present study reports that the suppression of SPARC expression by human melanoma cells using a SPARC antisense expression vector results in a significant decrease in the in vitro adhesive and invasive capacities of tumor cells, completely abolishing their in vivo tumorigenicity [6].
  • The cDNA encodes a secreted acidic calcium-binding glycoprotein of 664 aa residues, designated hevin, exhibiting 62% identity with the antiadhesive extracellular matrix protein SPARC, over a region of 232 aa spanning more than four fifths of the SPARC coding sequence [7].
  • Excess VEGF-A increased CNV before injury because VEGFR-1 activation was silenced by secreted protein, acidic and rich in cysteine (SPARC) [8].

Chemical compound and disease context of SPARC


Biological context of SPARC


Anatomical context of SPARC


Associations of SPARC with chemical compounds

  • 125I-PDGF-BB and -AB also bound specifically to SPARC that was immobilized on microtiter wells or bound to nitrocellulose after transfer from SDS/polyacrylamide gels [16].
  • We also detected an increased production of SPARC protein in the liver of animals treated with carbon tetrachloride [9].
  • Moreover, an additional diminution of VEGF activity by SPARC is accomplished through a reduction in the tyrosine phosphorylation of mitogen-activated protein kinases [15].
  • The common region of loss in these three 5q- syndrome patients includes the macrophage colony-stimulating factor-1 receptor (CSF1R), secreted protein, acidic, cysteine-rich (SPARC), and glutamate receptor (GR1A1) genes [19].
  • We have previously shown that angiogenesis, as reflected by fibrovascular invasion into subcutaneously implanted polyvinyl alcohol (PVA) sponges, is increased in SPARC-null mice (6-9 months of age) relative to their wild-type (WT) counterparts [20].

Physical interactions of SPARC


Regulatory relationships of SPARC


Other interactions of SPARC

  • Previous studies have localized the TCOF1 locus between D5S519 (proximal) and SPARC (distal), a region of 22 centirays as estimated by radiation hybrid mapping [32].
  • Expression of osteonectin was also associated with reduced adhesion to vitronectin, but not to fibronectin [1].
  • METHODS: Fibroblasts from skin biopsy specimens of 2 normal individuals were transfected with siRNA of SPARC and siRNA of CTGF [33].
  • CONCLUSIONS: SPARC or its combination with GPC3 is thus considered a potentially useful tumor marker, especially for melanoma at an early stage [34].
  • Adding transforming growth factor-beta (TGF-beta) decreased laminin and ALPase levels, whereas it increased SPARC and fibronectin levels 3- to 10-fold [26].

Analytical, diagnostic and therapeutic context of SPARC


  1. Osteonectin/SPARC induction by ectopic beta(3) integrin in human radial growth phase primary melanoma cells. Sturm, R.A., Satyamoorthy, K., Meier, F., Gardiner, B.B., Smit, D.J., Vaidya, B., Herlyn, M. Cancer Res. (2002) [Pubmed]
  2. Enhanced expression of SPARC/osteonectin in the tumor-associated stroma of non-small cell lung cancer is correlated with markers of hypoxia/acidity and with poor prognosis of patients. Koukourakis, M.I., Giatromanolaki, A., Brekken, R.A., Sivridis, E., Gatter, K.C., Harris, A.L., Sage, E.H. Cancer Res. (2003) [Pubmed]
  3. Secreted protein acidic and rich in cysteine produced by human melanoma cells modulates polymorphonuclear leukocyte recruitment and antitumor cytotoxic capacity. Alvarez, M.J., Prada, F., Salvatierra, E., Bravo, A.I., Lutzky, V.P., Carbone, C., Pitossi, F.J., Chuluyan, H.E., Podhajcer, O.L. Cancer. Res. (2005) [Pubmed]
  4. Gene expression profiling of low-grade diffuse astrocytomas by cDNA arrays. Huang, H., Colella, S., Kurrer, M., Yonekawa, Y., Kleihues, P., Ohgaki, H. Cancer Res. (2000) [Pubmed]
  5. Osteonectin, a bone-specific protein linking mineral to collagen. Termine, J.D., Kleinman, H.K., Whitson, S.W., Conn, K.M., McGarvey, M.L., Martin, G.R. Cell (1981) [Pubmed]
  6. Suppression of SPARC expression by antisense RNA abrogates the tumorigenicity of human melanoma cells. Ledda, M.F., Adris, S., Bravo, A.I., Kairiyama, C., Bover, L., Chernajovsky, Y., Mordoh, J., Podhajcer, O.L. Nat. Med. (1997) [Pubmed]
  7. Cloning from purified high endothelial venule cells of hevin, a close relative of the antiadhesive extracellular matrix protein SPARC. Girard, J.P., Springer, T.A. Immunity (1995) [Pubmed]
  8. Loss of SPARC-mediated VEGFR-1 suppression after injury reveals a novel antiangiogenic activity of VEGF-A. Nozaki, M., Sakurai, E., Raisler, B.J., Baffi, J.Z., Witta, J., Ogura, Y., Brekken, R.A., Sage, E.H., Ambati, B.K., Ambati, J. J. Clin. Invest. (2006) [Pubmed]
  9. Expression of SPARC in normal and fibrotic livers. Frizell, E., Liu, S.L., Abraham, A., Ozaki, I., Eghbali, M., Sage, E.H., Zern, M.A. Hepatology (1995) [Pubmed]
  10. The expression of SPARC in adipose tissue and its increased plasma concentration in patients with coronary artery disease. Takahashi, M., Nagaretani, H., Funahashi, T., Nishizawa, H., Maeda, N., Kishida, K., Kuriyama, H., Shimomura, I., Maeda, K., Hotta, K., Ouchi, N., Kihara, S., Nakamura, T., Yamashita, S., Matsuzawa, Y. Obes. Res. (2001) [Pubmed]
  11. SPARC is expressed in renal interstitial fibrosis and in renal vascular injury. Pichler, R.H., Hugo, C., Shankland, S.J., Reed, M.J., Bassuk, J.A., Andoh, T.F., Lombardi, D.M., Schwartz, S.M., Bennett, W.M., Alpers, C.E., Sage, E.H., Johnson, R.J., Couser, W.G. Kidney Int. (1996) [Pubmed]
  12. Aberrant expression of SPARC and its impact on proliferation and apoptosis in ADPKD cyst-lining epithelia. Wang, W., Mei, C., Tang, B., Zhao, H., Xu, C., Li, Z., Shen, X., Fu, W., Dai, B. Nephrol. Dial. Transplant. (2006) [Pubmed]
  13. Effect of resveratrol on matrix metalloproteinase-2 (MMP-2) and Secreted Protein Acidic and Rich in Cysteine (SPARC) on human cultured glioblastoma cells. Gagliano, N., Moscheni, C., Torri, C., Magnani, I., Bertelli, A.A., Gioia, M. Biomed. Pharmacother. (2005) [Pubmed]
  14. Narrowing the position of the Treacher Collins syndrome locus to a small interval between three new microsatellite markers at 5q32-33.1. Dixon, M.J., Dixon, J., Houseal, T., Bhatt, M., Ward, D.C., Klinger, K., Landes, G.M. Am. J. Hum. Genet. (1993) [Pubmed]
  15. SPARC (BM-40, osteonectin) inhibits the mitogenic effect of vascular endothelial growth factor on microvascular endothelial cells. Kupprion, C., Motamed, K., Sage, E.H. J. Biol. Chem. (1998) [Pubmed]
  16. The extracellular glycoprotein SPARC interacts with platelet-derived growth factor (PDGF)-AB and -BB and inhibits the binding of PDGF to its receptors. Raines, E.W., Lane, T.F., Iruela-Arispe, M.L., Ross, R., Sage, E.H. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  17. Osteonectin/SPARC/BM-40 in human decidua and carcinoma, tissues characterized by de novo formation of basement membrane. Wewer, U.M., Albrechtsen, R., Fisher, L.W., Young, M.F., Termine, J.D. Am. J. Pathol. (1988) [Pubmed]
  18. Enhancement of SPARC (osteonectin) synthesis in arthritic cartilage. Increased levels in synovial fluids from patients with rheumatoid arthritis and regulation by growth factors and cytokines in chondrocyte cultures. Nakamura, S., Kamihagi, K., Satakeda, H., Katayama, M., Pan, H., Okamoto, H., Noshiro, M., Takahashi, K., Yoshihara, Y., Shimmei, M., Okada, Y., Kato, Y. Arthritis Rheum. (1996) [Pubmed]
  19. Molecular cytogenetic delineation of the critical deleted region in the 5q- syndrome. Jaju, R.J., Boultwood, J., Oliver, F.J., Kostrzewa, M., Fidler, C., Parker, N., McPherson, J.D., Morris, S.W., Müller, U., Wainscoat, J.S., Kearney, L. Genes Chromosomes Cancer (1998) [Pubmed]
  20. Enhanced angiogenesis characteristic of SPARC-null mice disappears with age. Reed, M.J., Bradshaw, A.D., Shaw, M., Sadoun, E., Han, N., Ferara, N., Funk, S., Puolakkainen, P., Sage, E.H. J. Cell. Physiol. (2005) [Pubmed]
  21. Complex formation of human thrombospondin with osteonectin. Clezardin, P., Malaval, L., Ehrensperger, A.S., Delmas, P.D., Dechavanne, M., McGregor, J.L. Eur. J. Biochem. (1988) [Pubmed]
  22. Osteonectin in matrix remodeling. A plasminogen-osteonectin-collagen complex. Kelm, R.J., Swords, N.A., Orfeo, T., Mann, K.G. J. Biol. Chem. (1994) [Pubmed]
  23. Crystal structure of a pair of follistatin-like and EF-hand calcium-binding domains in BM-40. Hohenester, E., Maurer, P., Timpl, R. EMBO J. (1997) [Pubmed]
  24. Differential modulation of cell adhesion by interaction between adhesive and counter-adhesive proteins: characterization of the binding of vitronectin to osteonectin (BM40, SPARC). Rosenblatt, S., Bassuk, J.A., Alpers, C.E., Sage, E.H., Timpl, R., Preissner, K.T. Biochem. J. (1997) [Pubmed]
  25. Novel Function of Alternatively Activated Macrophages: Stabilin-1-Mediated Clearance of SPARC. Kzhyshkowska, J., Workman, G., Cardó-Vila, M., Arap, W., Pasqualini, R., Gratchev, A., Krusell, L., Goerdt, S., Sage, E.H. J. Immunol. (2006) [Pubmed]
  26. Differential effects of various growth factors and cytokines on the syntheses of DNA, type I collagen, laminin, fibronectin, osteonectin/secreted protein, acidic and rich in cysteine (SPARC), and alkaline phosphatase by human pulp cells in culture. Shiba, H., Fujita, T., Doi, N., Nakamura, S., Nakanishi, K., Takemoto, T., Hino, T., Noshiro, M., Kawamoto, T., Kurihara, H., Kato, Y. J. Cell. Physiol. (1998) [Pubmed]
  27. Differential effects of growth factors and cytokines on the synthesis of SPARC, DNA, fibronectin and alkaline phosphatase activity in human periodontal ligament cells. Fujita, T., Shiba, H., Van Dyke, T.E., Kurihara, H. Cell Biol. Int. (2004) [Pubmed]
  28. SPARC stimulates the synthesis of OPG/OCIF, MMP-2 and DNA in human periodontal ligament cells. Fujita, T., Shiba, H., Sakata, M., Uchida, Y., Nakamura, S., Kurihara, H. J. Oral Pathol. Med. (2002) [Pubmed]
  29. Molecular pathway for cancer metastasis to bone. De, S., Chen, J., Narizhneva, N.V., Heston, W., Brainard, J., Sage, E.H., Byzova, T.V. J. Biol. Chem. (2003) [Pubmed]
  30. Targeting SPARC expression decreases glioma cellular survival and invasion associated with reduced activities of FAK and ILK kinases. Shi, Q., Bao, S., Song, L., Wu, Q., Bigner, D.D., Hjelmeland, A.B., Rich, J.N. Oncogene (2007) [Pubmed]
  31. Proteomic analysis identified N-cadherin, clusterin, and HSP27 as mediators of SPARC (secreted protein, acidic and rich in cysteines) activity in melanoma cells. Sosa, M.S., Girotti, M.R., Salvatierra, E., Prada, F., de Olmo, J.A., Gallango, S.J., Albar, J.P., Podhajcer, O.L., Llera, A.S. Proteomics (2007) [Pubmed]
  32. A YAC contig encompassing the Treacher Collins syndrome critical region at 5q31.3-32. Dixon, J., Gladwin, A.J., Loftus, S.K., Riley, J.H., Perveen, R., Wasmuth, J.J., Anand, R., Dixon, M.J. Am. J. Hum. Genet. (1994) [Pubmed]
  33. SPARC, an upstream regulator of connective tissue growth factor in response to transforming growth factor beta stimulation. Zhou, X.D., Xiong, M.M., Tan, F.K., Guo, X.J., Arnett, F.C. Arthritis Rheum. (2006) [Pubmed]
  34. Highly sensitive detection of melanoma at an early stage based on the increased serum secreted protein acidic and rich in cysteine and glypican-3 levels. Ikuta, Y., Nakatsura, T., Kageshita, T., Fukushima, S., Ito, S., Wakamatsu, K., Baba, H., Nishimura, Y. Clin. Cancer Res. (2005) [Pubmed]
  35. Characterization of MAST9/Hevin, a SPARC-like protein, that is down-regulated in non-small cell lung cancer. Bendik, I., Schraml, P., Ludwig, C.U. Cancer Res. (1998) [Pubmed]
  36. Immunolocalization of SPARC, tenascin, and thrombospondin in pulmonary fibrosis. Kuhn, C., Mason, R.J. Am. J. Pathol. (1995) [Pubmed]
  37. Small interfering RNA inhibition of SPARC attenuates the profibrotic effect of transforming growth factor beta1 in cultured normal human fibroblasts. Zhou, X., Tan, F.K., Guo, X., Wallis, D., Milewicz, D.M., Xue, S., Arnett, F.C. Arthritis Rheum. (2005) [Pubmed]
  38. Effects of basic fibroblast growth factor on proliferation, the expression of osteonectin (SPARC) and alkaline phosphatase, and calcification in cultures of human pulp cells. Shiba, H., Nakamura, S., Shirakawa, M., Nakanishi, K., Okamoto, H., Satakeda, H., Noshiro, M., Kamihagi, K., Katayama, M., Kato, Y. Dev. Biol. (1995) [Pubmed]
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