1. ¹Hematology and BMT Center, University of Parma, Parma, Italy
2. ²Department of Pathology, University of Parma, Parma, Italy
3. ³Department of Clinical Science, University of Parma, Parma, Italy
4. ⁴Department of Internal Medicine and Biomedical Science, University of Parma, Parma, Italy

Correspondence: Dr N Giuliani, Hematology and BMT Center, Department of Internal Medicine and Biomedical Science, University of Parma, via Gramsci 14, 43100 Parma, Italy. Fax: +39 052 129 2765; E-mail: N_giuliani@yahoo.com or Nicola.Giuliani@unipr.it

Received 7 January 2005; Accepted 15 July 2005; Published online 6 October 2005.

Abstract

Osteopontin (OPN) is a multifunctional bone matrix glycoprotein that is involved in angiogenesis, cell survival and tumor progression. In this study we show that human myeloma cells directly produce OPN and express its major regulating gene Runx2/Cbfa1. The activity of Runx2/Cbfa1 protein in human myeloma cells has also been demonstrated. Moreover, using small interfering RNA (siRNA) to silent Runx2 in myeloma cells, we suppressed OPN mRNA and protein expression. OPN production in myeloma cells was stimulated by growth factors as IL-6 and IFG-1 and in turn OPN stimulated myeloma cell proliferation. In an 'in vitro' angiogenesis system we showed that OPN production by myeloma cells is critical for the proangiogenic effect of myeloma cells. The expression of OPN by purified bone marrow (BM) CD138⁺ cells has also been investigated in 60 newly diagnosed multiple myeloma (MM) patients, finding that 40% of MM patients tested expressed OPN. Higher OPN levels have been detected in the BM plasma of MM patients positive for OPN as compared to controls. Moreover, significantly higher BM angiogenesis has been observed in MM patients positive for OPN as compared to those negative. Our data highlight that human myeloma cells with active Runx2/Cbfa1 protein directly produce OPN that is involved in the pathophysiology of MM-induced angiogenesis.