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Dentine matrix protein 1 (DMP-1) is a marker of bone formation and mineralisation in soft tissue tumours

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Abstract

Dentine matrix protein 1 (DMP-1) is a non-collagenous matrix protein found in dentine and bone. It is highly expressed by osteocytes and has been identified in primary benign and malignant osteogenic bone tumours. Bone formation and matrix mineralisation are seen in a variety of benign and malignant soft tissue tumours and tumour-like lesions, and in this study, we analysed immunohistochemically the DMP-1 expression in a wide range of soft tissue lesions (n = 254) in order to assess whether DMP-1 expression is useful in the histological diagnosis of soft tissue tumours. Matrix staining of DMP-1 was seen in all cases of myositis ossificans, fibro-osseous tumour of the digits, extraskeletal soft tissue osteosarcoma and in most cases of ossifying fibromyxoid tumour. DMP-1 was also noted in dense collagenous connective tissue of mineralising soft tissue lesions such as tumoural calcinosis, dermatomyositis and calcific tendinitis. DMP-1 was expressed in areas of focal ossification and calcification in synovial sarcoma and other soft tissue tumours. With few exceptions, DMP-1 was not expressed in other benign and malignant soft tissue tumours. Our findings indicate that DMP-1 is a matrix marker of bone formation and mineralisation in soft tissue tumours. DMP-1 expression should be particularly useful in distinguishing extraskeletal osteosarcoma and ossifying fibromyxoid tumour from other sarcomas and in identifying areas of osteoid/bone formation and mineralisation in soft tissue tumours.

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References

  1. Bonewald LF (2007) Osteocytes. In: Marcus D, Nelson D, Rosen C (eds) Osteoprosis. Elsevier, San Diego, pp 169–190

    Google Scholar 

  2. Bonewald LF (2013) Osteocytes. In: Rosen CJ (ed) Prim. metab. bone dis. disord. miner. metab, 8th edn. Wiley-Blackwell, Hoboken, pp 34–41

    Chapter  Google Scholar 

  3. Qin C, Baba O, Butler WT (2004) Post-translational modifications of sibling proteins and their roles in osteogenesis and dentinogenesis. Crit Rev Oral Biol Med 15:126–136

    Article  CAS  PubMed  Google Scholar 

  4. Silvent J, Nassif N, Helary C et al (2013) Collagen osteoid-like model allows kinetic gene expression studies of non-collagenous proteins in relation with mineral development to understand bone biomineralization. PLoS One 8:e57344. doi:10.1371/journal.pone.0057344

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  5. Schiavi SC (2006) Bone talk. Nat Genet 38:1230–1231. doi:10.1038/ng1106-1230

    Article  CAS  PubMed  Google Scholar 

  6. Narayanan K, Ramachandran A, Hao J et al (2003) Dual functional roles of dentin matrix protein 1. Implications in biomineralization and gene transcription by activation of intracellular Ca2+ store. J Biol Chem 278:17500–17508. doi:10.1074/jbc.M212700200

    Article  CAS  PubMed  Google Scholar 

  7. Dallas SL, Bonewald LF (2010) Dynamics of the transition from osteoblast to osteocyte. Ann N Y Acad Sci 1192:437–443. doi:10.1111/j.1749-6632.2009.05246.×

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  8. Fisher LW, Fedarko NS (2003) Six genes expressed in bones and teeth encode the current members of the SIBLING family of proteins. Connect Tissue Res 44(Suppl 1):33–40

    Article  CAS  PubMed  Google Scholar 

  9. Fisher LW, Jain A, Tayback M, Fedarko NS (2004) Small integrin binding ligand N-linked glycoprotein gene family expression in different cancers. Clin Cancer Res 10:8501–8511. doi:10.1158/1078-0432.ccr-04-1072

    Article  CAS  PubMed  Google Scholar 

  10. Eapen A, Sundivakkam P, Song Y et al (2010) Calcium-mediated stress kinase activation by DMP1 promotes osteoblast differentiation. J Biol Chem 285:36339–36351. doi:10.1074/jbc.M110.145607

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  11. Narayanan K, Ramachandran A, Hao J, George A (2002) Transcriptional regulation of dentin matrix protein 1 (DMP1) by AP-1 (c-fos/c-jun) factors. Connect Tissue Res 43:365–371

    Article  CAS  PubMed  Google Scholar 

  12. Gajjeraman S, Narayanan K, Hao J et al (2007) Matrix macromolecules in hard tissues control the nucleation and hierarchical assembly of hydroxyapatite. J Biol Chem 282:1193–1204. doi:10.1074/jbc.M604732200

    Article  CAS  PubMed  Google Scholar 

  13. Feng JQ, Ward LM, Liu S et al (2006) Loss of DMP1 causes rickets and osteomalacia and identifies a role for osteocytes in mineral metabolism. Nat Genet 38:1310–1315. doi:10.1038/ng1905

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  14. Lorenz-Depiereux B, Bastepe M, Benet-Pages A et al (2006) DMP1 mutations in autosomal recessive hypophosphatemia implicate a bone matrix protein in the regulation of phosphate homeostasis. Nat Genet 38:1248–1250. doi:10.1038/ng1868

    Article  CAS  PubMed  Google Scholar 

  15. Kashima TG, Dongre A, Oppermann U, Athanasou NA (2013) Dentine matrix protein 1 (DMP-1) is a marker of bone-forming tumours. Virchows Arch 462:583–591. doi:10.1007/s00428-013-1399-z

    Article  CAS  PubMed  Google Scholar 

  16. Fletcher CDM, Bridge JA, Hogendoorn PCW, Mertens F (2013) WHO classification of tumours of soft tissue and bone. IARC, Lyon

    Google Scholar 

  17. Fanburg-Smith JC, Murphy MD (2010) Cartilage- and bone-forming tumors and tumor-like lesions. In: Miettinen M (ed) Mod. soft tissue pathol. Cambridge University Press, Cambridge, pp 862–895

    Chapter  Google Scholar 

  18. Weiss SW, Goldblum JR (2008) Osseous soft tissue tumors. In: Weiss SW, Goldblum JR (eds) Soft tissue tumors. Mosby Elsevier, Philadelphia, pp 1039–1062

    Google Scholar 

  19. Morozov A, Downey RJ, Healey J et al (2010) Benign mesenchymal stromal cells in human sarcomas. Clin Cancer Res 16:5630–5640. doi:10.1158/1078-0432.ccr-09-2886

    Article  CAS  PubMed  Google Scholar 

  20. Vigorita VJ (2008) Skeletal and extraskeletal calcification and ossification syndromes. Orthop. pathol. Lippincott Williams & Wilkins, Philadelphia, pp 50–103

    Google Scholar 

  21. Rosenberg AE (2013) Extraskeletal osteosarcoma. In: Fletcher CDM, Bridge JA, Hogendoorn PCW, Mertens F (eds) WHO classif. tumours soft tissue bone. IARC, Lyon, pp 161–162

    Google Scholar 

  22. Miettinen M (2010) Myxomas and ossifying fibromyxoid tumor. In: Miettinen M (ed) Mod. soft tissue pathol. Cambridge University Press, Cambridge, pp 325–334

    Chapter  Google Scholar 

  23. Miettinen MM, H.K, Weiss SW (2013) Ossifying fibromyxoid tumour. In: Fletcher CDM, Bridge JA, Hogendoorn PCW, Mertens F (eds) WHO classif. tumours soft tissue bone. IARC, Lyon, pp 206–207

  24. Feng JQ, Huang H, Lu Y et al (2003) The dentin matrix protein 1 (DMP1) is specifically expressed in mineralized, but not soft, tissues during development. J Dent Res 82:776–780

    Article  CAS  PubMed  Google Scholar 

  25. Golub EE (2011) Biomineralization and matrix vesicles in biology and pathology. Semin Immunopathol 33:409–417. doi:10.1007/s00281-010-0230-z

    Article  PubMed Central  PubMed  Google Scholar 

  26. Kirsch T (2012) Biomineralization—an active or passive process? Connect Tissue Res 53:438–445. doi:10.3109/03008207.2012.730081

    Article  CAS  PubMed  Google Scholar 

  27. He G, George A (2004) Dentin matrix protein 1 immobilized on type I collagen fibrils facilitates apatite deposition in vitro. J Biol Chem 279:11649–11656. doi:10.1074/jbc.M309296200

    Article  CAS  PubMed  Google Scholar 

  28. Toyosawa S, Tomita Y, Kishino M et al (2004) Expression of dentin matrix protein 1 in tumors causing oncogenic osteomalacia. Mod Pathol 17:573–578. doi:10.1038/modpathol.3800084

    Article  CAS  PubMed  Google Scholar 

  29. Naka N, Takenaka S, Araki N et al (2010) Synovial sarcoma is a stem cell malignancy. Stem Cells 28:1119–1131. doi:10.1002/stem.452

    CAS  PubMed  Google Scholar 

  30. Chaplet M, De Leval L, Waltregny D et al (2003) Dentin matrix protein 1 is expressed in human lung cancer. J Bone Miner Res 18:1506–1512. doi:10.1359/jbmr.2003.18.8.1506

    Article  CAS  PubMed  Google Scholar 

  31. Karadag A, Fedarko NS, Fisher LW (2005) Dentin matrix protein 1 enhances invasion potential of colon cancer cells by bridging matrix metalloproteinase-9 to integrins and CD44. Cancer Res 65:11545–11552. doi:10.1158/0008-5472.can-05-2861

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  32. Fen JQ, Zhang J, Dallas SL et al (2002) Dentin matrix protein 1, a target molecule for Cbfa1 in bone, is a unique bone marker gene. J Bone Miner Res 17:1822–1831. doi:10.1359/jbmr.2002.17.10.1822

    Article  PubMed  Google Scholar 

  33. Toyosawa S, Shintani S, Fujiwara T et al (2001) Dentin matrix protein 1 is predominantly expressed in chicken and rat osteocytes but not in osteoblasts. J Bone Miner Res 16:2017–2026. doi:10.1359/jbmr.2001.16.11.2017

    Article  CAS  PubMed  Google Scholar 

  34. Yoshikawa H, Rettig WJ, Lane JM et al (1994) Immunohistochemical detection of bone morphogenetic proteins in bone and soft-tissue sarcomas. Cancer 74:842–847

    Article  CAS  PubMed  Google Scholar 

  35. Fanburg-Smith JC, Bratthauer GL, Miettinen M (1999) Osteocalcin and osteonectin immunoreactivity in extraskeletal osteosarcoma: a study of 28 cases. Hum Pathol 30:32–38

    Article  CAS  PubMed  Google Scholar 

  36. Huang W, Yang S, Shao J, Li YP (2007) Signaling and transcriptional regulation in osteoblast commitment and differentiation. Front Biosci 12:3068–3092

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  37. Conner JR, Hornick JL (2013) SATB2 is a novel marker of osteoblastic differentiation in bone and soft tissue tumours. Histopathology 63:36–49. doi:10.1111/his.12138

    Article  PubMed  Google Scholar 

  38. Chung J, Lau J, Cheng LS et al (2010) SATB2 augments ΔNp63α in head and neck squamous cell carcinoma. EMBO Rep 11:777–783. doi:10.1038/embor.2010.125

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  39. Dragomir A, de Wit M, Johansson C et al (2014) The role of SATB2 as a diagnostic marker for tumors of colorectal origin: results of a pathology-based clinical prospective study. Am J Clin Pathol 141:630–638. doi:10.1309/ajcpww2urz9jkqju

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

The authors acknowledge the support of the Oxford NIHR BRU, The Sasakawa Foundation, The Rosetrees Trust, Sarcoma (UK) and The Bone Cancer Research Trust. This paper is dedicated to the memory of Takeshi Kashima, who first identified the utility of DMP-1 in bone and soft tissue tumour diagnosis.

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There is no conflict of interest with regard to this manuscript.

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Correspondence to N. A. Athanasou.

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Inagaki, Y., Kashima, T.G., Hookway, E.S. et al. Dentine matrix protein 1 (DMP-1) is a marker of bone formation and mineralisation in soft tissue tumours. Virchows Arch 466, 445–452 (2015). https://doi.org/10.1007/s00428-014-1706-3

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  • DOI: https://doi.org/10.1007/s00428-014-1706-3

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