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. 1992 Oct;3(10):1169–1180. doi: 10.1091/mbc.3.10.1169

Expression and distribution of osteopontin in human tissues: widespread association with luminal epithelial surfaces.

L F Brown 1, B Berse 1, L Van de Water 1, A Papadopoulos-Sergiou 1, C A Perruzzi 1, E J Manseau 1, H F Dvorak 1, D R Senger 1
PMCID: PMC275680  PMID: 1421573

Abstract

Osteopontin, a glycoprotein with a glycine-arginine-glycine-aspartate-serine (GRGDS) cell-binding domain, has been described in bone and is also known to be expressed in other organs, particularly kidney. The goal of the present work was to define the distribution of osteopontin synthesis and deposition in a wide variety of normal adult human tissues using a multifaceted approach that included immunohistochemistry, in situ hybridization, and Northern analysis. Immunohistochemical studies have revealed the unexpected finding that osteopontin is deposited as a prominent layer at the luminal surfaces of specific populations of epithelial cells of the gastrointestinal tract, gall bladder, pancreas, urinary and reproductive tracts, lung, breast, salivary glands, and sweat glands. Northern analyses identified gallbladder as a major site of osteopontin gene transcription comparable in magnitude with that of kidney, and immunoblotting identified osteopontin in bile. In situ hybridization localized osteopontin gene transcripts predominantly to the epithelium of a variety of organs as well as to ganglion cells of bowel wall. Osteopontin of epithelial cell origin, like bone-derived osteopontin, promoted GRGDS-dependent cell spreading in attachment assays. We postulate that osteopontin secreted by epithelium binds integrins on luminal surfaces. Collectively, these findings suggest an important role for osteopontin on many luminal epithelial surfaces communicating with the external environment.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Berse B., Brown L. F., Van de Water L., Dvorak H. F., Senger D. R. Vascular permeability factor (vascular endothelial growth factor) gene is expressed differentially in normal tissues, macrophages, and tumors. Mol Biol Cell. 1992 Feb;3(2):211–220. doi: 10.1091/mbc.3.2.211. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Chang P. L., Prince C. W. 1 alpha,25-dihydroxyvitamin D3 stimulates synthesis and secretion of nonphosphorylated osteopontin (secreted phosphoprotein 1) in mouse JB6 epidermal cells. Cancer Res. 1991 Apr 15;51(8):2144–2150. [PubMed] [Google Scholar]
  3. Chen J., Zhang Q., McCulloch C. A., Sodek J. Immunohistochemical localization of bone sialoprotein in foetal porcine bone tissues: comparisons with secreted phosphoprotein 1 (SPP-1, osteopontin) and SPARC (osteonectin). Histochem J. 1991 Jun;23(6):281–289. doi: 10.1007/BF01045047. [DOI] [PubMed] [Google Scholar]
  4. Craig A. M., Denhardt D. T. The murine gene encoding secreted phosphoprotein 1 (osteopontin): promoter structure, activity, and induction in vivo by estrogen and progesterone. Gene. 1991 Apr;100:163–171. doi: 10.1016/0378-1119(91)90362-f. [DOI] [PubMed] [Google Scholar]
  5. Craig A. M., Smith J. H., Denhardt D. T. Osteopontin, a transformation-associated cell adhesion phosphoprotein, is induced by 12-O-tetradecanoylphorbol 13-acetate in mouse epidermis. J Biol Chem. 1989 Jun 5;264(16):9682–9689. [PubMed] [Google Scholar]
  6. Falkow S. Bacterial entry into eukaryotic cells. Cell. 1991 Jun 28;65(7):1099–1102. doi: 10.1016/0092-8674(91)90003-h. [DOI] [PubMed] [Google Scholar]
  7. Fet V., Dickinson M. E., Hogan B. L. Localization of the mouse gene for secreted phosphoprotein 1 (Spp-1) (2ar, osteopontin, bone sialoprotein 1, 44-kDa bone phosphoprotein, tumor-secreted phosphoprotein) to chromosome 5, closely linked to Ric (Rickettsia resistance). Genomics. 1989 Aug;5(2):375–377. doi: 10.1016/0888-7543(89)90074-8. [DOI] [PubMed] [Google Scholar]
  8. Giachelli C., Bae N., Lombardi D., Majesky M., Schwartz S. Molecular cloning and characterization of 2B7, a rat mRNA which distinguishes smooth muscle cell phenotypes in vitro and is identical to osteopontin (secreted phosphoprotein I, 2aR). Biochem Biophys Res Commun. 1991 Jun 14;177(2):867–873. doi: 10.1016/0006-291x(91)91870-i. [DOI] [PubMed] [Google Scholar]
  9. Hynes R. O. Integrins: versatility, modulation, and signaling in cell adhesion. Cell. 1992 Apr 3;69(1):11–25. doi: 10.1016/0092-8674(92)90115-s. [DOI] [PubMed] [Google Scholar]
  10. Isberg R. R. Discrimination between intracellular uptake and surface adhesion of bacterial pathogens. Science. 1991 May 17;252(5008):934–938. doi: 10.1126/science.1674624. [DOI] [PubMed] [Google Scholar]
  11. Isberg R. R., Leong J. M. Multiple beta 1 chain integrins are receptors for invasin, a protein that promotes bacterial penetration into mammalian cells. Cell. 1990 Mar 9;60(5):861–871. doi: 10.1016/0092-8674(90)90099-z. [DOI] [PubMed] [Google Scholar]
  12. Jin C. H., Miyaura C., Ishimi Y., Hong M. H., Sato T., Abe E., Suda T. Interleukin 1 regulates the expression of osteopontin mRNA by osteoblasts. Mol Cell Endocrinol. 1990 Dec 21;74(3):221–228. doi: 10.1016/0303-7207(90)90227-y. [DOI] [PubMed] [Google Scholar]
  13. Kiefer M. C., Bauer D. M., Barr P. J. The cDNA and derived amino acid sequence for human osteopontin. Nucleic Acids Res. 1989 Apr 25;17(8):3306–3306. doi: 10.1093/nar/17.8.3306. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kubota T., Zhang Q., Wrana J. L., Ber R., Aubin J. E., Butler W. T., Sodek J. Multiple forms of SppI (secreted phosphoprotein, osteopontin) synthesized by normal and transformed rat bone cell populations: regulation by TGF-beta. Biochem Biophys Res Commun. 1989 Aug 15;162(3):1453–1459. doi: 10.1016/0006-291x(89)90837-1. [DOI] [PubMed] [Google Scholar]
  15. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  16. Mark M. P., Prince C. W., Gay S., Austin R. L., Butler W. T. 44-kDal bone phosphoprotein (osteopontin) antigenicity at ectopic sites in newborn rats: kidney and nervous tissues. Cell Tissue Res. 1988 Jan;251(1):23–30. doi: 10.1007/BF00215443. [DOI] [PubMed] [Google Scholar]
  17. Miyauchi A., Alvarez J., Greenfield E. M., Teti A., Grano M., Colucci S., Zambonin-Zallone A., Ross F. P., Teitelbaum S. L., Cheresh D. Recognition of osteopontin and related peptides by an alpha v beta 3 integrin stimulates immediate cell signals in osteoclasts. J Biol Chem. 1991 Oct 25;266(30):20369–20374. [PubMed] [Google Scholar]
  18. Miyazaki Y., Setoguchi M., Yoshida S., Higuchi Y., Akizuki S., Yamamoto S. The mouse osteopontin gene. Expression in monocytic lineages and complete nucleotide sequence. J Biol Chem. 1990 Aug 25;265(24):14432–14438. [PubMed] [Google Scholar]
  19. Moore M. A., Gotoh Y., Rafidi K., Gerstenfeld L. C. Characterization of a cDNA for chicken osteopontin: expression during bone development, osteoblast differentiation, and tissue distribution. Biochemistry. 1991 Mar 5;30(9):2501–2508. doi: 10.1021/bi00223a029. [DOI] [PubMed] [Google Scholar]
  20. Nagata T., Todescan R., Goldberg H. A., Zhang Q., Sodek J. Sulphation of secreted phosphoprotein I (SPPI, osteopontin) is associated with mineralized tissue formation. Biochem Biophys Res Commun. 1989 Nov 30;165(1):234–240. doi: 10.1016/0006-291x(89)91059-0. [DOI] [PubMed] [Google Scholar]
  21. Nemir M., DeVouge M. W., Mukherjee B. B. Normal rat kidney cells secrete both phosphorylated and nonphosphorylated forms of osteopontin showing different physiological properties. J Biol Chem. 1989 Oct 25;264(30):18202–18208. [PubMed] [Google Scholar]
  22. Noda M., Vogel R. L., Craig A. M., Prahl J., DeLuca H. F., Denhardt D. T. Identification of a DNA sequence responsible for binding of the 1,25-dihydroxyvitamin D3 receptor and 1,25-dihydroxyvitamin D3 enhancement of mouse secreted phosphoprotein 1 (SPP-1 or osteopontin) gene expression. Proc Natl Acad Sci U S A. 1990 Dec;87(24):9995–9999. doi: 10.1073/pnas.87.24.9995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Nomura S., Wills A. J., Edwards D. R., Heath J. K., Hogan B. L. Developmental expression of 2ar (osteopontin) and SPARC (osteonectin) RNA as revealed by in situ hybridization. J Cell Biol. 1988 Feb;106(2):441–450. doi: 10.1083/jcb.106.2.441. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Oldberg A., Franzén A., Heinegård D. Cloning and sequence analysis of rat bone sialoprotein (osteopontin) cDNA reveals an Arg-Gly-Asp cell-binding sequence. Proc Natl Acad Sci U S A. 1986 Dec;83(23):8819–8823. doi: 10.1073/pnas.83.23.8819. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Patarca R., Freeman G. J., Singh R. P., Wei F. Y., Durfee T., Blattner F., Regnier D. C., Kozak C. A., Mock B. A., Morse H. C., 3rd Structural and functional studies of the early T lymphocyte activation 1 (Eta-1) gene. Definition of a novel T cell-dependent response associated with genetic resistance to bacterial infection. J Exp Med. 1989 Jul 1;170(1):145–161. doi: 10.1084/jem.170.1.145. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Prince C. W., Butler W. T. 1,25-Dihydroxyvitamin D3 regulates the biosynthesis of osteopontin, a bone-derived cell attachment protein, in clonal osteoblast-like osteosarcoma cells. Coll Relat Res. 1987 Sep;7(4):305–313. doi: 10.1016/s0174-173x(87)80036-5. [DOI] [PubMed] [Google Scholar]
  27. Prince C. W., Dickie D., Krumdieck C. L. Osteopontin, a substrate for transglutaminase and factor XIII activity. Biochem Biophys Res Commun. 1991 Jun 28;177(3):1205–1210. doi: 10.1016/0006-291x(91)90669-x. [DOI] [PubMed] [Google Scholar]
  28. Reinholt F. P., Hultenby K., Oldberg A., Heinegård D. Osteopontin--a possible anchor of osteoclasts to bone. Proc Natl Acad Sci U S A. 1990 Jun;87(12):4473–4475. doi: 10.1073/pnas.87.12.4473. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Ruoslahti E., Hayman E. G., Pierschbacher M., Engvall E. Fibronectin: purification, immunochemical properties, and biological activities. Methods Enzymol. 1982;82(Pt A):803–831. doi: 10.1016/0076-6879(82)82103-4. [DOI] [PubMed] [Google Scholar]
  30. Ruoslahti E. Integrins. J Clin Invest. 1991 Jan;87(1):1–5. doi: 10.1172/JCI114957. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Senger D. R., Perruzzi C. A., Gracey C. F., Papadopoulos A., Tenen D. G. Secreted phosphoproteins associated with neoplastic transformation: close homology with plasma proteins cleaved during blood coagulation. Cancer Res. 1988 Oct 15;48(20):5770–5774. [PubMed] [Google Scholar]
  32. Senger D. R., Perruzzi C. A., Papadopoulos A. Elevated expression of secreted phosphoprotein I (osteopontin, 2ar) as a consequence of neoplastic transformation. Anticancer Res. 1989 Sep-Oct;9(5):1291–1299. [PubMed] [Google Scholar]
  33. Senger D. R., Perruzzi C. A., Papadopoulos A., Tenen D. G. Purification of a human milk protein closely similar to tumor-secreted phosphoproteins and osteopontin. Biochim Biophys Acta. 1989 Jun 13;996(1-2):43–48. doi: 10.1016/0167-4838(89)90092-7. [DOI] [PubMed] [Google Scholar]
  34. Shiraga H., Min W., VanDusen W. J., Clayman M. D., Miner D., Terrell C. H., Sherbotie J. R., Foreman J. W., Przysiecki C., Neilson E. G. Inhibition of calcium oxalate crystal growth in vitro by uropontin: another member of the aspartic acid-rich protein superfamily. Proc Natl Acad Sci U S A. 1992 Jan 1;89(1):426–430. doi: 10.1073/pnas.89.1.426. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Singh K., DeVouge M. W., Mukherjee B. B. Physiological properties and differential glycosylation of phosphorylated and nonphosphorylated forms of osteopontin secreted by normal rat kidney cells. J Biol Chem. 1990 Oct 25;265(30):18696–18701. [PubMed] [Google Scholar]
  36. Singh R. P., Patarca R., Schwartz J., Singh P., Cantor H. Definition of a specific interaction between the early T lymphocyte activation 1 (Eta-1) protein and murine macrophages in vitro and its effect upon macrophages in vivo. J Exp Med. 1990 Jun 1;171(6):1931–1942. doi: 10.1084/jem.171.6.1931. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Somerman M. J., Prince C. W., Butler W. T., Foster R. A., Moehring J. M., Sauk J. J. Cell attachment activity of the 44 kilodalton bone phosphoprotein is not restricted to bone cells. Matrix. 1989 Jan;9(1):49–54. doi: 10.1016/s0934-8832(89)80018-6. [DOI] [PubMed] [Google Scholar]
  38. Swanson G. J., Nomura S., Hogan B. L. Distribution of expression of 2AR (osteopontin) in the embryonic mouse inner ear revealed by in situ hybridisation. Hear Res. 1989 Sep;41(2-3):169–177. doi: 10.1016/0378-5955(89)90008-7. [DOI] [PubMed] [Google Scholar]
  39. Ullrich O., Mann K., Haase W., Koch-Brandt C. Biosynthesis and secretion of an osteopontin-related 20-kDa polypeptide in the Madin-Darby canine kidney cell line. J Biol Chem. 1991 Feb 25;266(6):3518–3525. [PubMed] [Google Scholar]
  40. Weinstein I. B., Orenstein J. M., Gebert R., Kaighn M. E., Stadler U. C. Growth and structural properties of epithelial cell cultures established from normal rat liver and chemically induced hepatomas. Cancer Res. 1975 Jan;35(1):253–263. [PubMed] [Google Scholar]
  41. Wrana J. L., Zhang Q., Sodek J. Full length cDNA sequence of porcine secreted phosphoprotein-I (SPP-I, osteopontin). Nucleic Acids Res. 1989 Dec 11;17(23):10119–10119. doi: 10.1093/nar/17.23.10119. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Yoon K., Buenaga R., Rodan G. A. Tissue specificity and developmental expression of rat osteopontin. Biochem Biophys Res Commun. 1987 Nov 13;148(3):1129–1136. doi: 10.1016/s0006-291x(87)80250-4. [DOI] [PubMed] [Google Scholar]
  43. Young M. F., Kerr J. M., Termine J. D., Wewer U. M., Wang M. G., McBride O. W., Fisher L. W. cDNA cloning, mRNA distribution and heterogeneity, chromosomal location, and RFLP analysis of human osteopontin (OPN). Genomics. 1990 Aug;7(4):491–502. doi: 10.1016/0888-7543(90)90191-v. [DOI] [PubMed] [Google Scholar]
  44. Zhang Q., Domenicucci C., Goldberg H. A., Wrana J. L., Sodek J. Characterization of fetal porcine bone sialoproteins, secreted phosphoprotein I (SPPI, osteopontin), bone sialoprotein, and a 23-kDa glycoprotein. Demonstration that the 23-kDa glycoprotein is derived from the carboxyl terminus of SPPI. J Biol Chem. 1990 May 5;265(13):7583–7589. [PubMed] [Google Scholar]

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