The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

SPP1  -  secreted phosphoprotein 1

Homo sapiens

Synonyms: BNSP, BSPI, Bone sialoprotein 1, ETA-1, Nephropontin, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of SPP1


Psychiatry related information on SPP1

  • BACKGROUND: This study was undertaken to ascertain the effect of dietary modification on urinary stone risks, and to determine whether the response depends on the prevailing urinary calcium [10].
  • In contrast, oscillating fluid flow predicted to occur in the lacunar-canalicular system due to routine physical activities (2 N/m2, 1 Hz) caused significant increases in both Ca2+i and OPN mRNA [11].
  • Plasma osteopontin levels were significantly increased in individuals with HIV-associated dementia [12].

High impact information on SPP1

  • Expression of OPN is enhanced by a variety of toxicants, especially those that activate protein kinase C. In its capacity as a signaling molecule, OPN can modify gene expression and promote the migration of monocytes/macrophages up an OPN gradient [13].
  • Elevated OPN expression often correlates with malignancy and has been shown to enhance the tumorigenic and/or metastatic phenotype of the cancer cell [13].
  • Recent studies have revealed that OPN plays critical roles in bone remodeling and cell-mediated immunity [13].
  • Osteopontin (OPN) is a glycosylated phosphoprotein found in all body fluids and in the proteinaceous matrix of mineralized tissues [13].
  • Extensive research has elucidated the pivotal role of OPN in regulating the cell signaling that controls tumor progression and metastasis [14].

Chemical compound and disease context of SPP1

  • We have recently reported that osteopontin (OPN) stimulates cell motility and nuclear factor kappaB-mediated secretion of urokinase-type plasminogen activator (uPA) through phosphatidylinositol 3-kinase/Akt signaling pathways in breast cancer cells (Das, R., Mahabeleshwar, G. H., and Kundu, G. C. (2003) J. Biol. Chem. 278, 28593-28606) [2].
  • AIM: Osteopontin (OPN) is a phosphorylated glycoprotein with diverse functions including cancer development, progression and metastasis [15].
  • I have utilized a recombinant E. coli expression system to obtain milligram quantities of human bone sialoprotein and human osteopontin that may be used to study extracellular matrix protein interactions with hydroxyapatite [16].
  • SPP1 gene polymorphisms have been shown to be associated with several immune inflammatory diseases including multiple sclerosis (MS), which is characterized by fewer allergic symptoms and lower numbers of allergen sensitizations [17].
  • In addition to already known tumor-associated genes, the majority of identified genes have not yet been brought into context with tumorigenesis such as genes involved in bone matrix mineralization (OSN, OPN, and OSF-2) in lung, breast, and kidney cancer or genes controlling Ca(2+) homeostasis (RCN1,CALCA, S100 protein family) [18].

Biological context of SPP1

  • Osteopontin (SPP1) is a soluble ligand with pleomorphic immunologic activities including activation of macrophage chemotaxis, promotion of Th1 responses, and activation of B1 B cells [19].
  • High levels of OPN gene expression were also detected in 2- to 3-week-old primary LTCs [20].
  • When CD34+ cells were cultured in the presence of purified OPN, tyrosine phosphorylation of a 34-kDa molecule was increased 2- to 3-fold, an effect that was diminished in the presence of an OPN neutralizing monoclonal antibody [20].
  • Expression of the bone sialoprotein (BSP) gene, a marker of bone formation, is largely restricted to cells in mineralized tissues [21].
  • In the present study, we show that osteopontin (OPN), a proinflammatory mediator involved in tissue repair, induces IL-1beta up-regulation in human monocytes [22].

Anatomical context of SPP1

  • Like other endometrial cell lines, ECC-1 cells express the steroid receptor coactivators and exhibit epidermal growth factor-stimulated expression of known luminal proteins thought to be involved in implantation, including the hyaluronate receptor CD44 and SPP1 (formerly osteopontin) and CD55 (decay-accelerating factor) [23].
  • In fact, when the cells were incubated in the presence of monensin during the adhesion assay, they still adhered but spreading did not occur, focal adhesions disappeared and BSP, OPN, and FN were accumulated in intracellular granules [24].
  • Using Transwells we determined that stromal cells were secreting a factor that up-regulated OPN gene expression in CD14+ cells [20].
  • In conclusion, OPN-activated monocytes may contribute to the onset of angiogenesis through a mechanism mediated by IL-1beta [22].
  • Accordingly, rIL-1beta mimicked the proangiogenic activity of OPN-treated monocyte supernatants, and IL-1R (type I) was found to be expressed in the chorioallantoic membrane [22].

Associations of SPP1 with chemical compounds


Physical interactions of SPP1

  • OPN binds to several integrins and CD44 variants [31].
  • The role of SRF in the activation of the ternary complex might be to bind to the ETA-1 domain, somehow conceal it's activation domain and in the process unmask the ETA-2 domain (for phosphorylation by MAP kinases) and activate transcription [32].

Regulatory relationships of SPP1


Other interactions of SPP1


Analytical, diagnostic and therapeutic context of SPP1


  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. Osteopontin induces AP-1-mediated secretion of urokinase-type plasminogen activator through c-Src-dependent epidermal growth factor receptor transactivation in breast cancer cells. Das, R., Mahabeleshwar, G.H., Kundu, G.C. J. Biol. Chem. (2004) [Pubmed]
  3. Osteopontin but not osteonectin messenger RNA expression is a prognostic marker in curatively resected non-small cell lung cancer. Schneider, S., Yochim, J., Brabender, J., Uchida, K., Danenberg, K.D., Metzger, R., Schneider, P.M., Salonga, D., Hölscher, A.H., Danenberg, P.V. Clin. Cancer Res. (2004) [Pubmed]
  4. Expression of bone-related protein messenger RNA in human meningiomas: possible involvement of osteopontin in development of psammoma bodies. Hirota, S., Nakajima, Y., Yoshimine, T., Kohri, K., Nomura, S., Taneda, M., Hayakawa, T., Kitamura, Y. J. Neuropathol. Exp. Neurol. (1995) [Pubmed]
  5. Human myeloma cells express the bone regulating gene Runx2/Cbfa1 and produce osteopontin that is involved in angiogenesis in multiple myeloma patients. Colla, S., Morandi, F., Lazzaretti, M., Rizzato, R., Lunghi, P., Bonomini, S., Mancini, C., Pedrazzoni, M., Crugnola, M., Rizzoli, V., Giuliani, N. Leukemia (2005) [Pubmed]
  6. Plasma osteopontin levels and expression in adipose tissue are increased in obesity. Gómez-Ambrosi, J., Catalán, V., Ramírez, B., Rodríguez, A., Colina, I., Silva, C., Rotellar, F., Mugueta, C., Gil, M.J., Cienfuegos, J.A., Salvador, J., Frühbeck, G. J. Clin. Endocrinol. Metab. (2007) [Pubmed]
  7. Osteopontin and interleukin-8 expression is independently associated with prostate cancer recurrence. Caruso, D.J., Carmack, A.J., Lokeshwar, V.B., Duncan, R.C., Soloway, M.S., Lokeshwar, B.L. Clin. Cancer Res. (2008) [Pubmed]
  8. Activation of the osteopontin/matrix metalloproteinase-9 pathway correlates with prostate cancer progression. Castellano, G., Malaponte, G., Mazzarino, M.C., Figini, M., Marchese, F., Gangemi, P., Travali, S., Stivala, F., Canevari, S., Libra, M. Clin. Cancer Res. (2008) [Pubmed]
  9. Gene expression profiling of paraffin-embedded primary melanoma using the DASL assay identifies increased osteopontin expression as predictive of reduced relapse-free survival. Conway, C., Mitra, A., Jewell, R., Randerson-Moor, J., Lobo, S., Nsengimana, J., Edward, S., Sanders, D.S., Cook, M., Powell, B., Boon, A., Elliott, F., de Kort, F., Knowles, M.A., Bishop, D.T., Newton-Bishop, J. Clin. Cancer Res. (2009) [Pubmed]
  10. Effect of dietary modification on urinary stone risk factors. Pak, C.Y., Odvina, C.V., Pearle, M.S., Sakhaee, K., Peterson, R.D., Poindexter, J.R., Brinkley, L.J. Kidney Int. (2005) [Pubmed]
  11. Substrate deformation levels associated with routine physical activity are less stimulatory to bone cells relative to loading-induced oscillatory fluid flow. You, J., Yellowley, C.E., Donahue, H.J., Zhang, Y., Chen, Q., Jacobs, C.R. Journal of biomechanical engineering. (2000) [Pubmed]
  12. Osteopontin is increased in HIV-associated dementia. Burdo, T.H., Ellis, R.J., Fox, H.S. J. Infect. Dis. (2008) [Pubmed]
  13. Role of osteopontin in cellular signaling and toxicant injury. Denhardt, D.T., Giachelli, C.M., Rittling, S.R. Annu. Rev. Pharmacol. Toxicol. (2001) [Pubmed]
  14. Osteopontin: role in cell signaling and cancer progression. Rangaswami, H., Bulbule, A., Kundu, G.C. Trends Cell Biol. (2006) [Pubmed]
  15. Enhancement of osteopontin expression in HepG2 cells by epidermal growth factor via phosphatidylinositol 3-kinase signaling pathway. Zhang, G.X., Zhao, Z.Q., Wang, H.D., Hao, B. World J. Gastroenterol. (2004) [Pubmed]
  16. Generation and use of recombinant human bone sialoprotein and osteopontin for hydroxyapatite studies. Stubbs, J.T. Connect. Tissue Res. (1996) [Pubmed]
  17. Sequence variants of the secreted phosphoprotein 1 gene are associated with total serum immunoglobulin E levels in a Japanese population. Tanino, Y., Hizawa, N., Konno, S., Fukui, Y., Takahashi, D., Maeda, Y., Huang, S.K., Nishimura, M. Clin. Exp. Allergy (2006) [Pubmed]
  18. Tissue-wide expression profiling using cDNA subtraction and microarrays to identify tumor-specific genes. Amatschek, S., Koenig, U., Auer, H., Steinlein, P., Pacher, M., Gruenfelder, A., Dekan, G., Vogl, S., Kubista, E., Heider, K.H., Stratowa, C., Schreiber, M., Sommergruber, W. Cancer Res. (2004) [Pubmed]
  19. An osteopontin (SPP1) polymorphism is associated with systemic lupus erythematosus. Forton, A.C., Petri, M.A., Goldman, D., Sullivan, K.E. Hum. Mutat. (2002) [Pubmed]
  20. Human marrow stromal cells activate monocytes to secrete osteopontin, which down-regulates Notch1 gene expression in CD34+ cells. Iwata, M., Awaya, N., Graf, L., Kahl, C., Torok-Storb, B. Blood (2004) [Pubmed]
  21. 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]
  22. Cutting Edge: IL-1beta Mediates the Proangiogenic Activity of Osteopontin-Activated Human Monocytes. Naldini, A., Leali, D., Pucci, A., Morena, E., Carraro, F., Nico, B., Ribatti, D., Presta, M. J. Immunol. (2006) [Pubmed]
  23. ECC-1 cells: a well-differentiated steroid-responsive endometrial cell line with characteristics of luminal epithelium. Mo, B., Vendrov, A.E., Palomino, W.A., DuPont, B.R., Apparao, K.B., Lessey, B.A. Biol. Reprod. (2006) [Pubmed]
  24. Osteocalcin induces chemotaxis, secretion of matrix proteins, and calcium-mediated intracellular signaling in human osteoclast-like cells. Chenu, C., Colucci, S., Grano, M., Zigrino, P., Barattolo, R., Zambonin, G., Baldini, N., Vergnaud, P., Delmas, P.D., Zallone, A.Z. J. Cell Biol. (1994) [Pubmed]
  25. Age-related changes in human bone proteoglycan structure. Impact of osteogenesis imperfecta. Grzesik, W.J., Frazier, C.R., Shapiro, J.R., Sponseller, P.D., Robey, P.G., Fedarko, N.S. J. Biol. Chem. (2002) [Pubmed]
  26. Bone Sialoprotein Enhances Migration of Bone Marrow Stromal Cells Through Matrices by Bridging MMP-2 to alpha(v)beta(3)-Integrin. Karadag, A., Fisher, L.W. J. Bone Miner. Res. (2006) [Pubmed]
  27. Osteopontin-induced migration of human mammary epithelial cells involves activation of EGF receptor and multiple signal transduction pathways. Tuck, A.B., Hota, C., Wilson, S.M., Chambers, A.F. Oncogene (2003) [Pubmed]
  28. Inhibition of osteoblast differentiation but not adipocyte differentiation of mesenchymal stem cells by sera obtained from aged females. Abdallah, B.M., Haack-Sørensen, M., Fink, T., Kassem, M. Bone (2006) [Pubmed]
  29. Thrombin hydrolysis of human osteopontin is dependent on thrombin anion-binding exosites. Myles, T., Leung, L.L. J. Biol. Chem. (2008) [Pubmed]
  30. Polymeric osteopontin employs integrin alpha9beta1 as a receptor and attracts neutrophils by presenting a de novo binding site. Nishimichi, N., Higashikawa, F., Kinoh, H.H., Tateishi, Y., Matsuda, H., Yokosaki, Y. J. Biol. Chem. (2009) [Pubmed]
  31. Vascular endothelial growth factor and osteopontin in tumor biology. Shijubo, N., Uede, T., Kon, S., Nagata, M., Abe, S. Critical reviews in oncogenesis. (2000) [Pubmed]
  32. Transcriptional activation domains of elk-1, delta elk-1 and SAP-1 proteins. Bhattacharya, G., Lee, L., Reddy, E.S., Rao, V.N. Oncogene (1993) [Pubmed]
  33. HGF and M-CSF modulate adhesion of MDA-231 breast cancer cell by increasing osteopontin secretion. Grano, M., Mori, G., Minielli, V., Colucci, S., Vaira, S., Giannelli, G., Martemucci, S., Giorgino, F., Zallone, A.Z. J. Biol. Regul. Homeost. Agents (2002) [Pubmed]
  34. Specifically modified osteopontin in rheumatoid arthritis fibroblast-like synoviocytes supports interaction with B cells and enhances production of interleukin-6. Take, Y., Nakata, K., Hashimoto, J., Tsuboi, H., Nishimoto, N., Ochi, T., Yoshikawa, H. Arthritis Rheum. (2009) [Pubmed]
  35. Three SIBLINGs (small integrin-binding ligand, N-linked glycoproteins) enhance factor H's cofactor activity enabling MCP-like cellular evasion of complement-mediated attack. Jain, A., Karadag, A., Fohr, B., Fisher, L.W., Fedarko, N.S. J. Biol. Chem. (2002) [Pubmed]
  36. 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]
  37. Role of osteopontin in induction of monocyte chemoattractant protein 1 and macrophage inflammatory protein 1beta through the NF-kappaB and MAPK pathways in rheumatoid arthritis. Zheng, W., Li, R., Pan, H., He, D., Xu, R., Guo, T.B., Guo, Y., Zhang, J.Z. Arthritis Rheum. (2009) [Pubmed]
  38. Proteomics-based validation of genomic data: applications in colorectal cancer diagnosis. Madoz-Gúrpide, J., López-Serra, P., Martínez-Torrecuadrada, J.L., Sánchez, L., Lombardía, L., Casal, J.I. Mol. Cell Proteomics (2006) [Pubmed]
WikiGenes - Universities