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

Abstract

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-1alpha (SDF-1alpha) in peripheral blood plasma are associated with osteolysis in multiple myeloma patients. We have now examined whether SDF-1alpha levels also correlate with angiogenesis. We examined the contribution of multiple myeloma plasma cell-derived SDF-1alpha 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-1alpha levels, respectively. We show that multiple myeloma plasma cell line-derived conditioned medium containing SDF-1alpha 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-1alpha. We now extend these observations and show the novel finding that peripheral blood plasma levels of SDF-1alpha positively correlate with the degree of bone marrow angiogenesis in multiple myeloma and monoclonal gammopathy of undetermined significance patients. High levels of SDF-1alpha produced by multiple myeloma plasma cells promote osteolysis and bone marrow angiogenesis. Therefore, we propose that inhibition of SDF-1alpha may be an effective mechanism by which angiogenesis and osteolysis can be reduced in multiple myeloma patients.