title: Brain-derived neurotrophic factor promotes growth and migration of multiple myeloma cells.
abstract: The evolution of multiple myeloma (MM) depends on complex signals from the bone marrow microenvironment, which support proliferation and survival of malignant plasma cells. Previous study defined a brain-derived neurotrophic factor-tyrosine kinase receptor B (BDNF/TrkB) axis in myeloma and autocrine growth stimulation by BDNF in various tumor cells. We examined the biological effects of BDNF on MM cells. Using a reverse transcriptase-polymerase chain reaction, Western blotting, and immunohistochemistry, we observed that both BDNF and its high-affinity receptor TrkB are expressed by MM cell lines (RPMI 8226, U266, and KM3) and primary MM cells. Functional studies revealed that BDNF was a potent growth factor for MM. BDNF (5-500 ng/mL) had strong proliferative effects on both MM cell lines and primary MM cells, shown by [(3)H]thymidine incorporation assay. BDNF (12.5-200 ng/mL) also induced migration of MM cells, as indicated by the Transwell migration assay. Together, our data indicate that BDNF is a potent myeloma growth and chemotactic factor and suggest that the BDNF/TrkB pathway is a potential therapeutic target in MM.
authors.affiliation: Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Dadao, Wuhan 430022, PR China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Hu
authors.forename: Chun-yan
authors.initials: CY
authors.lastname: Sun
authors.forename: Hua-fang
authors.initials: HF
authors.lastname: Wang
authors.forename: Tao
authors.initials: T
authors.lastname: Guo
authors.forename: Wen-ning
authors.initials: WN
authors.lastname: Wei
authors.forename: Ya-dan
authors.initials: YD
authors.lastname: Wang
authors.forename: Wen-juan
authors.initials: WJ
authors.lastname: He
authors.forename: Tao
authors.initials: T
authors.lastname: Wu
authors.forename: Hao
authors.initials: H
authors.lastname: Tan
authors.forename: Tang-chun
authors.initials: TC
authors.lastname: Wu
mesh_terms: D001483:Base Sequence; D015153:Blotting, Western; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D017931:DNA Primers; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007150:Immunohistochemistry; D009101:Multiple Myeloma / Q000473:pathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D017931:DNA Primers