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Gene Review

IBSP  -  integrin-binding sialoprotein

Homo sapiens

Synonyms: BNSP, BSP, BSP II, BSP-II, Bone sialoprotein 2, ...
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Disease relevance of IBSP

  • We hypothesize that breast cancer cell expression of phenotypic properties of skeletal cell types, including BSP as one component of that phenotype, is the result of ectopic expression or activity of one or more central transcriptional regulators of bone cell gene expression [1].
  • There is a significant clinical correlation between the expression of bone sialoprotein (BSP) and skeletal metastasis of breast cancers [1].
  • Recent studies have demonstrated that two SIBLING family members, bone sialoprotein (BSP) and osteopontin (OPN), are overexpressed in human prostate cancer [2].
  • The purpose of this study was to determine the role of BSP in the homing of cancer cells and to provide insights into the role of BSP in physiological as well as pathological processes [3].
  • Moderate to strong staining for BSP was observed in all (100%) carcinomas, which also expressed BSP mRNA as determined by in situ hybridization [4].

Psychiatry related information on IBSP

  • ALO is not a true apraxia; it constitutes an eyelid dystonia as shown by its clinical and electrophysiological features as well as pharmacological reactions and is encountered in a clinical spectrum ranging from an isolated form to predominant BSP [5].

High impact information on IBSP

  • BACKGROUND: Bone sialoprotein (BSP), a bone matrix protein, was recently found to be expressed ectopically in breast cancer and to have a statistically significant association with poor prognosis and the development of bone metastases in that disease [6].
  • CONCLUSIONS: To our knowledge, this study is the first to demonstrate BSP expression in human prostate cancer and to highlight the protein's statistically significant prognostic value in patients with clinically confined prostate adenocarcinomas [6].
  • Although 24 patients had hepatomegaly, and the majority had abnormalities of serum transaminases, alkaline phosphatase, and BSP clearance, only 3 had evidence of portal hypertension and complications of advanced liver disease [7].
  • In addition to BSP, the cloned oatp also mediated Na(+)-independent uptake of conjugated (taurocholate) and unconjugated (cholate) bile acids [8].
  • Expression of the endogenous BSP gene in Gallus osteoblasts was similarly downregulated by forced expression of Cbfa factors [9].

Chemical compound and disease context of IBSP


Biological context of IBSP

  • IBSP has been sublocalized by in situ hybridization to chromosome 4q28-q31 and is composed of six small exons (51 to 159 bp) and 1 large exon (approximately 2.6 kb) [15].
  • Although three genes, BMPR1B, PP1 and IBSP, are located to 4q21-q25 and their functions are related to bone morphogenesis, no mutations were identified by sequencing analysis of their exons [16].
  • Several characteristics, including the amino acid sequence, suggest that 59-kDa BSP may be the rat counterpart of human alpha 2-HSG [17].
  • Cell adhesion assays showed that the binding of BSP to cells can be reversibly diminished by denaturation [18].
  • We have produced full-length recombinant BSP in a human cell line and purified the protein from human bone retaining the native structure with proper folding and post-translational modifications [18].

Anatomical context of IBSP

  • However, rat 59-kDa BSP is a single peptide and synthesized by both osteoblasts and hepatocytes, whereas human alpha 2-HSG is known to be a heterodimer and to be synthesized by the liver [17].
  • But when newborn rat calvaria, primary cultures of osteoblast-rich cells, and adult rat hepatocytes were incubated with radioactive leucine, immunoreactive 59-kDa BSP was detected in their conditioned medium by fluorography [17].
  • Bone sialoprotein (BSP) is a major non-collagenous protein found almost exclusively in bone and other mineralized tissues including enamel, dentin and cementum [3].
  • The resultant cultured cells expressed different levels of hBSP as detected by RT-PCR and Western blot [3].
  • Osteopontin (OPN) and bone sialoprotein (BSP) are bone matrix proteins that have been implicated in the selective affinity of cancer cells for bone [19].

Associations of IBSP with chemical compounds

  • The affinity for hydroxyapatite was higher for bone-derived BSP than for recombinant BSP [18].
  • Bone sialoprotein (BSP) and osteopontin (OPN) are two members of the SIBLING (Small Integrin-Binding LIgand, N-linked Glycoprotein) family of genetically related proteins that are clustered on human chromosome 4 [20].
  • The antibody against human BSP II was significantly more active than all ASOs used and was equally active or even surpassed the activity of ibandronate and ErPC3 in all three assays [21].
  • Dentin has small amounts of OPN and BSP but also contains a major sialic acid-rich protein, DSP that has an overall composition similar to the bone sialoproteins [22].
  • These interactions involve HUVEC alpha(v)beta(3) integrin receptors and the RGD domain of BSP [23].

Other interactions of IBSP

  • Bone sialoprotein I has an amino-terminal sequence of NH2-Ile-Pro-Val-Lys-Gln-Ala. . . which is different from that of bone sialoprotein II with an amino-terminal sequence of NH2-Phe-Ser-Met-Lys-Asn-Leu. . . The two bone sialoproteins do not cross-react on Western blot analysis [24].
  • After 20 days culture in OM, BMP-2, BSP, and OP were more expressed in FGF/Dex than in CTR-expanded BMSC (mRNA levels were, respectively, 9.5-, 14.9-, and 5.8-fold higher), unlike all the other investigated genes [25].
  • Ten of them were already identified in odontoblasts such as DSPP, BSP, enamelysin and Col1A1 [26].
  • High-density cultures of human mesenchymal pre-osteoblastic cells (HEPM 1486, ATCC) were grown for 72 h and real-time PCR used for quantitative analysis of alkaline phosphatase (ALP), core-binding factor alpha1 (Cbfa1), Osterix, Type I Collagen, Osteocalcin and bone sialoprotein II gene expression [27].
  • RESULTS: The different surfaces did not alter the mRNA expression for ALP, type I collagen, osterix, osteocalcin, or BSP II [28].

Analytical, diagnostic and therapeutic context of IBSP


  1. Osteoblast-related transcription factors Runx2 (Cbfa1/AML3) and MSX2 mediate the expression of bone sialoprotein in human metastatic breast cancer cells. Barnes, G.L., Javed, A., Waller, S.M., Kamal, M.H., Hebert, K.E., Hassan, M.Q., Bellahcene, A., Van Wijnen, A.J., Young, M.F., Lian, J.B., Stein, G.S., Gerstenfeld, L.C. Cancer Res. (2003) [Pubmed]
  2. Expression of dentin sialophosphoprotein in human prostate cancer and its correlation with tumor aggressiveness. Chaplet, M., Waltregny, D., Detry, C., Fisher, L.W., Castronovo, V., Bellahcène, A. Int. J. Cancer (2006) [Pubmed]
  3. Over-expression of bone sialoprotein enhances bone metastasis of human breast cancer cells in a mouse model. Zhang, J.H., Tang, J., Wang, J., Ma, W., Zheng, W., Yoneda, T., Chen, J. Int. J. Oncol. (2003) [Pubmed]
  4. Expression of bone sialoprotein and osteopontin in breast cancer bone metastases. Ibrahim, T., Leong, I., Sanchez-Sweatman, O., Khokha, R., Sodek, J., Tenenbaum, H.C., Ganss, B., Cheifetz, S. Clin. Exp. Metastasis (2000) [Pubmed]
  5. "Apraxia of lid opening," a focal eyelid dystonia: clinical study of 32 patients. Krack, P., Marion, M.H. Mov. Disord. (1994) [Pubmed]
  6. Prognostic value of bone sialoprotein expression in clinically localized human prostate cancer. Waltregny, D., Bellahcène, A., Van Riet, I., Fisher, L.W., Young, M., Fernandez, P., Dewé, W., de Leval, J., Castronovo, V. J. Natl. Cancer Inst. (1998) [Pubmed]
  7. LIver abnormalities in patients with Gaucher's disease. James, S.P., Stromeyer, F.W., Chang, C., Barranger, J.A. Gastroenterology (1981) [Pubmed]
  8. Expression cloning of a rat liver Na(+)-independent organic anion transporter. Jacquemin, E., Hagenbuch, B., Stieger, B., Wolkoff, A.W., Meier, P.J. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  9. runt homology domain transcription factors (Runx, Cbfa, and AML) mediate repression of the bone sialoprotein promoter: evidence for promoter context-dependent activity of Cbfa proteins. Javed, A., Barnes, G.L., Jasanya, B.O., Stein, J.L., Gerstenfeld, L., Lian, J.B., Stein, G.S. Mol. Cell. Biol. (2001) [Pubmed]
  10. Characterization of native and recombinant bone sialoprotein: delineation of the mineral-binding and cell adhesion domains and structural analysis of the RGD domain. Stubbs, J.T., Mintz, K.P., Eanes, E.D., Torchia, D.A., Fisher, L.W. J. Bone Miner. Res. (1997) [Pubmed]
  11. Purification and fragmentation of nondenatured bone sialoprotein: evidence for a cryptic, RGD-resistant cell attachment domain. Mintz, K.P., Grzesik, W.J., Midura, R.J., Robey, P.G., Termine, J.D., Fisher, L.W. J. Bone Miner. Res. (1993) [Pubmed]
  12. A bone sialoprotein-binding protein from Staphylococcus aureus: a member of the staphylococcal Sdr family. Tung, H., Guss, B., Hellman, U., Persson, L., Rubin, K., Rydén, C. Biochem. J. (2000) [Pubmed]
  13. Bone sialoprotein is a specific biochemical marker of bone metabolism in postmenopausal women: a randomized 1-year study. Störk, S., Störk, C., Angerer, P., Kothny, W., Schmitt, P., Wehr, U., von Schacky, C., Rambeck, W. Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. (2000) [Pubmed]
  14. Serum bone sialoprotein: a marker of bone resorption in postmenopausal osteoporosis. Shaarawy, M., Hasan, M. Scand. J. Clin. Lab. Invest. (2001) [Pubmed]
  15. The human bone sialoprotein gene (IBSP): genomic localization and characterization. Kerr, J.M., Fisher, L.W., Termine, J.D., Wang, M.G., McBride, O.W., Young, M.F. Genomics (1993) [Pubmed]
  16. A novel locus for parietal foramina maps to chromosome 4q21-q23. Chen, G., Zhang, D., Feng, G., Liu, W., He, L. J. Hum. Genet. (2003) [Pubmed]
  17. Purification, characterization, and studies on biosynthesis of a 59-kDa bone sialic acid-containing protein (BSP) from rat mandible using a monoclonal antibody. Evidence that 59-kDa BSP may be the rat counterpart of human alpha 2-HS glycoprotein and is synthesized by both hepatocytes and osteoblasts. Ohnishi, T., Arakaki, N., Nakamura, O., Hirono, S., Daikuhara, Y. J. Biol. Chem. (1991) [Pubmed]
  18. Structural characterization of human recombinant and bone-derived bone sialoprotein. Functional implications for cell attachment and hydroxyapatite binding. Wuttke, M., Müller, S., Nitsche, D.P., Paulsson, M., Hanisch, F.G., Maurer, P. J. Biol. Chem. (2001) [Pubmed]
  19. Differential expression of osteopontin and bone sialoprotein in bone metastasis of breast and prostate carcinoma. Carlinfante, G., Vassiliou, D., Svensson, O., Wendel, M., Heinegård, D., Andersson, G. Clin. Exp. Metastasis (2003) [Pubmed]
  20. Flexible structures of SIBLING proteins, bone sialoprotein, and osteopontin. Fisher, L.W., Torchia, D.A., Fohr, B., Young, M.F., Fedarko, N.S. Biochem. Biophys. Res. Commun. (2001) [Pubmed]
  21. Decreased levels of osteopontin and bone sialoprotein II are correlated with reduced proliferation, colony formation, and migration of GFP-MDA-MB-231 cells. Adwan, H., Bäuerle, T., Najajreh, Y., Elazer, V., Golomb, G., Berger, M.R. Int. J. Oncol. (2004) [Pubmed]
  22. Sialoproteins of bone and dentin. Butler, W.T. Journal de biologie buccale. (1991) [Pubmed]
  23. Bone sialoprotein mediates human endothelial cell attachment and migration and promotes angiogenesis. Bellahcène, A., Bonjean, K., Fohr, B., Fedarko, N.S., Robey, F.A., Young, M.F., Fisher, L.W., Castronovo, V. Circ. Res. (2000) [Pubmed]
  24. Purification and partial characterization of small proteoglycans I and II, bone sialoproteins I and II, and osteonectin from the mineral compartment of developing human bone. Fisher, L.W., Hawkins, G.R., Tuross, N., Termine, J.D. J. Biol. Chem. (1987) [Pubmed]
  25. Real-time quantitative RT-PCR analysis of human bone marrow stromal cells during osteogenic differentiation in vitro. Frank, O., Heim, M., Jakob, M., Barbero, A., Schäfer, D., Bendik, I., Dick, W., Heberer, M., Martin, I. J. Cell. Biochem. (2002) [Pubmed]
  26. A substractive PCR-based cDNA library from human odontoblast cells: identification of novel genes expressed in tooth forming cells. Buchaille, R., Couble, M.L., Magloire, H., Bleicher, F. Matrix Biol. (2000) [Pubmed]
  27. Effects of implant surface microtopography on osteoblast gene expression. Masaki, C., Schneider, G.B., Zaharias, R., Seabold, D., Stanford, C. Clinical oral implants research. (2005) [Pubmed]
  28. Effects of fluoride-modified titanium surfaces on osteoblast proliferation and gene expression. Isa, Z.M., Schneider, G.B., Zaharias, R., Seabold, D., Stanford, C.M. The International journal of oral & maxillofacial implants. (2006) [Pubmed]
  29. Tumor cells are the source of osteopontin and bone sialoprotein expression in human breast cancer. Sharp, J.A., Sung, V., Slavin, J., Thompson, E.W., Henderson, M.A. Lab. Invest. (1999) [Pubmed]
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