This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Martin, S. K. Articles by Zannettino, A. C.W. Search for Related Content PubMed PubMed Citation Articles by Martin, S. K. Articles by Zannettino, A. C.W.

Tumor Angiogenesis Is Associated with Plasma Levels of Stromal-Derived Factor-1 in Patients with Multiple Myeloma

Authors' Affiliations: ¹ Myeloma and Mesenchymal Research Group, Matthew Roberts Foundation Laboratory, Division of Haematology, Institute of Medical and Veterinary Science, The Hanson Institute, and the Department of Medicine, University of Adelaide; ² Division of Haematology, The Institute of Medical and Veterinary Science; and ³ Mesenchymal Research Laboratory, Division of Haematology, Institute of Medical and Veterinary Science, The Hanson Institute, and University of Adelaide, Adelaide, Australia

Requests for reprints: Andrew C.W. Zannettino, Myeloma and Mesenchymal Research Group, Matthew Roberts Foundation Laboratory, Division of Haematology, Institute of Medical and Veterinary Science, P.O. Box 14, Rundle Mall, Adelaide 5000, Australia. Phone: 61-8-8222-3455; Fax: 61-8-8222-3139; E-mail: andrew.zannettino{at}imvs.sa.gov.au.

Purpose: Multiple myeloma is an incurable hematologic malignancy characterized by increased bone marrow angiogenesis and extensive lytic bone disease. We have previously shown that elevated levels of stromal-derived factor-1 (SDF-1) in peripheral blood plasma are associated with osteolysis in multiple myeloma patients. We have now examined whether SDF-1 levels also correlate with angiogenesis.

Experimental Design: We examined the contribution of multiple myeloma plasma cell–derived SDF-1 in the stimulation of in vitro angiogenesis using a tube formation assay. We also collected trephine and peripheral blood plasma samples from patients with multiple myeloma to analyze microvessel density and SDF-1 levels, respectively.

Results: We show that multiple myeloma plasma cell line–derived conditioned medium containing SDF-1 stimulates in vitro angiogenesis. In addition, in a large cohort of patients with multiple myeloma and its precursor condition monoclonal gammopathy of undetermined significance, we confirm previous findings that plasma cell burden correlates with both angiogenesis and plasma levels of SDF-1. We now extend these observations and show the novel finding that peripheral blood plasma levels of SDF-1 positively correlate with the degree of bone marrow angiogenesis in multiple myeloma and monoclonal gammopathy of undetermined significance patients.

Conclusions: High levels of SDF-1 produced by multiple myeloma plasma cells promote osteolysis and bone marrow angiogenesis. Therefore, we propose that inhibition of SDF-1 may be an effective mechanism by which angiogenesis and osteolysis can be reduced in multiple myeloma patients.