Brain-derived neurotrophic factor promotes growth and migration of multiple myeloma cells.
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.
Hu
Yu
Y
Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Dadao, Wuhan 430022, PR China.
Sun
Chun-yan
CY
Wang
Hua-fang
HF
Guo
Tao
T
Wei
Wen-ning
WN
Wang
Ya-dan
YD
He
Wen-juan
WJ
Wu
Tao
T
Tan
Hao
H
Wu
Tang-chun
TC
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
D019208:Brain-Derived Neurotrophic Factor; D017931:DNA Primers