Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Commentary
  • Published:

Osteopontin, angiogenesis and multiple myeloma

Leukemia volume 19, pages 2203–2205 (2005)Cite this article

The significance of Osteopontin (OPN) and angiogenesis in the pathogenesis and the progression of hematological malignancies is highlighted in a paper by Colla et al.1 In this article, Colla et al, expand their studies on bone marrow (BM) angiogenesis2, 3 in an attempt to describe the role of OPN in multiple myeloma (MM). In an in vitro angiogenesis assay system, authors demonstrate that conditioned media from MM cells has a proangiogenic effect and OPN is critical for this outcome (Figure 5). The Runt family of transcription factors (RUNX1/AML1, RUNX2 and RUNX3) can regulate OPN expression.4, 5, 6 By comparing the expression profiles and DNA-binding activity of RUNX1/AML1 and RUNX2 in primary and MM cell lines, the authors speculate that RUNX2 is a regulator of OPN expression in MM cells (Figure 2). Using small interfering RNA to silence RUNX2 expression in MM cells authors confirmed that indeed RUNX2 is indispensable for OPN expression (Figure 3). Their preliminary analysis with newly diagnosed MM patients highlights a strong correlation between active RUNX2/Cbfa1 protein expression with OPN production and BM angiogenesis.

OPN is a multifunctional Glyco phosphoprotein, highly expressed in bone as well as in various other cell types such as macrophages, endothelial cells, smooth muscles and epithelial cells.7 Initially, OPN was described as a major noncollagenous protein in bone, named bone sialoprotein8 and as a secreted phosphoprotein by transformed malignant epithelial cells.9 OPN also has a role in normal tissue remodeling processes such as bone resorption, angiogenesis, wound healing and tissue injury as well as certain diseases such as vascular restenosis, atherosclerosis and renal diseases.7 Several recent studies sited in this commentary shows OPNs role in various aspects of the formation and progression of MM.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

References

  1. Colla S, Morandi F, Lazzaretti M, Rizzato R, Lunghi P, Bonomini S et al. Human myeloma cells express the bone regulating gene RUNX2/CBFA1 and produce osteopontin that is involved in angiogenesis in multiple myeloma patients. Leukemia 2006 (in press).

  2. Giuliani N, Colla S, Lazzaretti M, Sala R, Roti G, Mancini C et al. Proangiogenic properties of human myeloma cells: production of angiopoietin-1 and its potential relationship to myeloma-induced angiogenesis. Blood 2003; 102: 638–645.

    Article  CAS  Google Scholar 

  3. Giuliani N, Colla S, Morandi F, Rizzoli V . Angiopoietin-1 and myeloma-induced angiogenesis. Leuk Lymphoma 2005; 46: 29–33.

    Article  CAS  Google Scholar 

  4. Inman CK, Shore P . The osteoblast transcription factor Runx2 is expressed in mammary epithelial cells and mediates osteopontin expression. J Biol Chem 2003; 278: 48684–48689.

    Article  CAS  Google Scholar 

  5. Wai PY, Kuo PC . The role of Osteopontin in tumor metastasis. J Surg Res 2004; 121: 228–241.

    Article  CAS  Google Scholar 

  6. Zheng H, Guo Z, Ma Q, Jia H, Dang G . Cbfa1/osf2 transduced bone marrow stromal cells facilitate bone formation in vitro and in vivo. Calcif Tissue Int 2004; 74: 194–203.

    Article  CAS  Google Scholar 

  7. Mazzali M, Kipari T, Ophascharoensuk V, Wesson JA, Johnson R, Hughes J . Osteopontin – a molecule for all seasons. QJM 2002; 95: 3–13.

    Article  CAS  Google Scholar 

  8. Franzen A, Heinegard D . Isolation and characterization of two sialoproteins present only in bone calcified matrix. Biochem J 1985; 232: 715–724.

    Article  CAS  Google Scholar 

  9. Senger DR, Wirth DF, Hynes RO . Transformed mammalian cells secrete specific proteins and phosphoproteins. Cell 1979; 16: 885–893.

    Article  CAS  Google Scholar 

  10. Hussein MA, Juturi JV, Lieberman I . Multiple myeloma: present and future. Curr Opin Oncol 2002; 14: 31–35.

    Article  Google Scholar 

  11. Hussein MA . New treatment strategies for multiple myeloma. Semin Hematol 2004; 41 (4 Suppl 7): 2–8.

    Article  CAS  Google Scholar 

  12. Hanahan D, Weinberg RA . The hallmarks of cancer. Cell 2000; 100: 57–70.

    Article  CAS  Google Scholar 

  13. Vacca A, Ribatti D, Roncali L, Ranieri G, Serio G, Silvestris F et al. Bone marrow angiogenesis and progression in multiple myeloma. Br J Haematol 1994; 87: 503–508.

    Article  CAS  Google Scholar 

  14. Asosingh K, De Raeve H, Menu E, Van Riet I, Van Marck E, Van Camp B et al. Angiogenic switch during 5T2MM murine myeloma tumorigenesis: role of CD45 heterogeneity. Blood 2004; 103: 3131–3137.

    Article  CAS  Google Scholar 

  15. Giuliani N, Colla S, Rizzoli V . Angiogenic switch in multiple myeloma. Hematology 2004; 9: 377–381.

    Article  CAS  Google Scholar 

  16. Bellamy WT . Expression of vascular endothelial growth factor and its receptors in multiple myeloma and other hematopoietic malignancies. Semin Oncol 2001; 28: 551–559.

    Article  CAS  Google Scholar 

  17. Bellamy WT . Vascular endothelial growth factor as a target opportunity in hematological malignancies. Curr Opin Oncol 2002; 14: 649–656.

    Article  CAS  Google Scholar 

  18. Podar K, Tai YT, Davies FE, Lentzsch S, Sattler M, Hideshima T et al. Vascular endothelial growth factor triggers signaling cascades mediating multiple myeloma cell growth and migration. Blood 2001; 98: 428–435.

    Article  CAS  Google Scholar 

  19. Kumar S, Witzig TE, Timm M, Haug J, Wellik L, Kimlinger TK et al. Bone marrow angiogenic ability and expression of angiogenic cytokines in myeloma: evidence favoring loss of marrow angiogenesis inhibitory activity with disease progression. Blood 2004; 104: 1159–1165.

    Article  CAS  Google Scholar 

  20. Saeki Y, Mima T, Ishii T, Ogata A, Kobayashi H, Ohshima S et al. Enhanced production of osteopontin in multiple myeloma: clinical and pathogenic implications. Br J Haematol 2003; 123: 263–270.

    Article  CAS  Google Scholar 

  21. Chellaiah MA, Kizer N, Biswas R, Alvarez U, Strauss-Schoenberger J, Rifas L et al. Osteopontin deficiency produces osteoclast dysfunction due to reduced CD44 surface expression. Mol Biol Cell 2003; 14: 173–189.

    Article  CAS  Google Scholar 

  22. Liaw L, Birk DE, Ballas CB, Whitsitt JS, Davidson JM, Hogan BL . Altered wound healing in mice lacking a functional osteopontin gene (spp1). J Clin Invest 1998; 101: 1468–1478.

    Article  CAS  Google Scholar 

  23. Rittling SR, Matsumoto HN, McKee MD, Nanci A, An XR, Novick KE et al. Mice lacking osteopontin show normal development and bone structure but display altered osteoclast formation in vitro. J Bone Miner Res 1998; 13: 1101–1111.

    Article  CAS  Google Scholar 

  24. Yoshitake H, Rittling SR, Denhardt DT, Noda M . Osteopontin-deficient mice are resistant to ovariectomy-induced bone resorption. Proc Natl Acad Sci USA 1999; 96: 8156–8160.

    Article  CAS  Google Scholar 

  25. Ishijima M, Rittling SR, Yamashita T, Tsuji K, Kurosawa H, Nifuji A et al. Enhancement of osteoclastic bone resorption and suppression of osteoblastic bone formation in response to reduced mechanical stress do not occur in the absence of osteopontin. J Exp Med 2001; 193: 399–404.

    Article  CAS  Google Scholar 

  26. Standal T, Borset M, Sundan A . Role of osteopontin in adhesion, migration, cell survival and bone remodeling. Exp Oncol 2004; 26: 179–184.

    CAS  PubMed  Google Scholar 

  27. Abe M, Hiura K, Wilde J, Shioyasono A, Moriyama K, Hashimoto T et al. Osteoclasts enhance myeloma cell growth and survival via cell–cell contact: a vicious cycle between bone destruction and myeloma expansion. Blood 2004; 104: 2484–2491.

    Article  CAS  Google Scholar 

  28. Standal T, Hjorth-Hansen H, Rasmussen T, Dahl IM, Lenhoff S, Brenne AT et al. Osteopontin is an adhesive factor for myeloma cells and is found in increased levels in plasma from patients with multiple myeloma. Haematologica 2004; 89: 174–182.

    CAS  PubMed  Google Scholar 

  29. Senger DR, Perruzzi CA, Papadopoulos-Sergiou A, Van de Water L . Adhesive properties of osteopontin: regulation by a naturally occurring thrombin-cleavage in close proximity to the GRGDS cell-binding domain. Mol Biol Cell 1994; 5: 565–574.

    Article  CAS  Google Scholar 

  30. Senger DR, Perruzzi CA . Cell migration promoted by a potent GRGDS-containing thrombin-cleavage fragment of osteopontin. Biochim Biophys Acta 1996; 1314: 13–24.

    Article  CAS  Google Scholar 

  31. Goodison S, Urquidi V, Tarin D . CD44 cell adhesion molecules. Mol Pathol 1999; 52: 189–196.

    Article  CAS  Google Scholar 

  32. Ashkar S, Weber GF, Panoutsakopoulou V, Sanchirico ME, Jansson M, Zawaideh S et al. Eta-1 (osteopontin): an early component of type-1 (cell-mediated) immunity. Science 2000; 287: 860–864.

    Article  CAS  Google Scholar 

  33. Gunthert U, Hofmann M, Rudy W, Reber S, Zoller M, Haussmann I et al. A new variant of glycoprotein CD44 confers metastatic potential to rat carcinoma cells. Cell 1991; 65: 13–24.

    Article  CAS  Google Scholar 

  34. Ponta H, Sherman L, Herrlich PA . CD44: from adhesion molecules to signalling regulators. Nat Rev Mol Cell Biol 2003; 4: 33–45.

    Article  CAS  Google Scholar 

  35. Rudy W, Hofmann M, Schwartz-Albiez R, Zoller M, Heider KH et al. The two major CD44 proteins expressed on a metastatic rat tumor cell line are derived from different splice variants: each one individually suffices to confer metastatic behavior. Cancer Res 1993; 53: 1262–1268.

    CAS  PubMed  Google Scholar 

  36. Ducy P, Zhang R, Geoffroy V, Ridall AL, Karsenty G . Osf2/Cbfa1: a transcriptional activator of osteoblast differentiation. Cell 1997; 89: 747–754.

    Article  CAS  Google Scholar 

  37. Komori T, Yagi H, Nomura S, Yamaguchi A, Sasaki K, Deguchi K et al. Targeted disruption of Cbfa1 results in a complete lack of bone formation owing to maturational arrest of osteoblasts. Cell 1997; 89: 755–764.

    Article  CAS  Google Scholar 

  38. Otto F, Thornell AP, Crompton T, Denzel A, Gilmour KC, Rosewell IR et al. Cbfa1, a candidate gene for cleidocranial dysplasia syndrome, is essential for osteoblast differentiation and bone development. Cell 1997; 89: 765–771.

    Article  CAS  Google Scholar 

  39. Ito Y . Oncogenic potential of the RUNX gene family: ‘overview’. Oncogene 2004; 23: 4198–4208.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank Dr Ernest C Borden and Barbara Jacobs for their critical reading of this commentary and valuable suggestions. This work is partially supported by an ACS pilot grant to VC.

Author information

Authors and Affiliations

  1. Project Scientist, The Cleveland Clinic Foundation, Taussig Cancer Center, Center for Hematology and Oncology Molecular Therapeutics, Cleveland, OH, USA

    V Cheriyath

  2. The Cleveland Clinic Foundation, Taussig Cancer Center, Multiple Myeloma Research Program, Cleveland, OH, USA

    V Cheriyath & M A Hussein

Authors
  1. V Cheriyath
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M A Hussein
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to V Cheriyath.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Cheriyath, V., Hussein, M. Osteopontin, angiogenesis and multiple myeloma. Leukemia 19, 2203–2205 (2005). https://doi.org/10.1038/sj.leu.2403978

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.leu.2403978

This article is cited by

Search

Advanced search

Quick links