OBJECTIVETo investigate the expression of brain-derived neurotrophic factor (BDNF) in multiple myeloma (MM) cells and the correlation between BDNF and MM angiogenesis.

METHODSThe expressions of BDNF mRNA transcripts and protein in MM cell lines (RPMI 8226, KM3) were determined by RT-PCR and Western blot, respectively, BDNF levels in culture supernatant by enzyme-linked immunosorbent assay. Proliferation of human umbilical vein endothelial cells (HUVEC) mixed with MM culture medium at different concentrations was examined by MTT assay. The effects of MM culture medium on HUVEC migration and tube formation were studied by modified Boyden chamber assay and tube formation assay, respectively.

RESULTSBDNF was expressed in and secreted by MM cell lines RPMI 8226 and KM3. BDNF concentrations in culture supernatants were within the range of its biological activity. MM culture medium induced a concentration-dependent proliferation of HUVEC. The number of HUVEC at a concentration of 50% KM3 culture medium and at full KM3 culture medium were (1.85 +/- 0.23)-fold and (2.16 +/- 0.29) -fold increase, respectively (P <0.05), compared with that of control. The proliferative activity of HUVEC was reduced on the addition of BDNF antibody to the culture medium. MM culture medium also stimulated the migration and differentiation of HUVEC in vitro, the chemotactic index of HUVEC at a concentration of 50% KM3 culture medium and at full KM3 culture medium were 1.85 +/- 0.23 and 2.16 +/- 0.29, respectively (P < 0.05). Full KM3 culture medium also stimulated capillary-like tube formation in HUVEC (P <0.01), and addition of anti-human BDNF antibody neutralized these effects significantly.

CONCLUSIONMM cell lines expressed and secreted biologically active BDNF, which may be involved, at least in part, in MM angiogenesis.