PMID- 17889702
OWN - NLM
STAT- MEDLINE
DCOM- 20071109
LR  - 20091119
IS  - 0165-4608 (Print)
IS  - 0165-4608 (Linking)
VI  - 178
IP  - 1
DP  - 2007 Oct 1
TI  - Identification of brain-derived neurotrophic factor as a novel angiogenic protein 
      in multiple myeloma.
PG  - 1-10
AB  - Patients with multiple myeloma (MM) have increased bone marrow angiogenesis, but 
      the angiogenic properties of myeloma cells and the mechanism of MM-induced 
      angiogenesis have not been completely clarified. The brain-derived neurotrophic 
      factor (BDNF) and its high-affinity receptor, TrkB, have been identified as 
      critical factors in the regulation of vessel formation. In this study, we 
      demonstrate that patients with MM had increased BDNF and vascular endothelial 
      growth factor (VEGF) in their peripheral blood. We also found in particular that 
      a decreased BDNF level was correlated with the remission of MM. BDNF was 
      expressed by the human myeloma cell line RPMI8226 and primary myeloma cells, and 
      TrkB was expressed by human umbilical vein endothelial cells (HUVEC) at the 
      protein levels. In a coculture system, we observed that both RPMI8226 cells and 
      primary myeloma cells induced the migration and formation of a net-like structure 
      in HUVEC. The anti-BDNF monoclonal antibody significantly but partially 
      restrained the angiogenesis effect of MM cells. Moreover, in an experimental 
      model of angiogenesis in vivo, BDNF and VEGF significantly promoted vessel 
      formation in Matrigel plug compared to the control. These effects were also 
      blocked by anti-BDNF monoclonal antibody. Finally, our in vitro results were 
      supported by the in vivo finding in human myeloma xenograft NOD/SCID models. 
      Anti-BDNF mAb treatment resulted in inhibition of tumor growth, decreased vessel 
      density, and tumor necrosis. Our study suggested that the BDNF/TrkB signaling 
      pathway could be involved, at least in part, in MM-induced angiogenesis.
FAU - Hu, Yu
AU  - Hu Y
AD  - Institute of Hematology, Union Hospital, Tongji Medical College, Huanzhong 
      University of Science and Technology, 1277 Jiefang Dadao, Wuhan 430022, P.R. 
      China. hillaryw27@yahoo.com.cn
FAU - Wang, Ya-dan
AU  - Wang YD
FAU - Guo, Tao
AU  - Guo T
FAU - Wei, Wen-ning
AU  - Wei WN
FAU - Sun, Chun-yan
AU  - Sun CY
FAU - Zhang, Lu
AU  - Zhang L
FAU - Huang, Jin
AU  - Huang J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cancer Genet Cytogenet
JT  - Cancer genetics and cytogenetics
JID - 7909240
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - EC 2.7.10.1 (Receptor, trkB)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Cell Line, Tumor
MH  - Female
MH  - Humans
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, SCID
MH  - Middle Aged
MH  - Models, Biological
MH  - Multiple Myeloma/*pathology
MH  - Neoplasm Transplantation
MH  - *Neovascularization, Pathologic
MH  - Receptor, trkB/metabolism
EDAT- 2007/09/25 09:00
MHDA- 2007/11/10 09:00
CRDT- 2007/09/25 09:00
PHST- 2007/02/19 00:00 [received]
PHST- 2007/05/13 00:00 [revised]
PHST- 2007/05/15 00:00 [accepted]
PHST- 2007/09/25 09:00 [pubmed]
PHST- 2007/11/10 09:00 [medline]
PHST- 2007/09/25 09:00 [entrez]
AID - S0165-4608(07)00326-3 [pii]
AID - 10.1016/j.cancergencyto.2007.05.028 [doi]
PST - ppublish
SO  - Cancer Genet Cytogenet. 2007 Oct 1;178(1):1-10. doi: 
      10.1016/j.cancergencyto.2007.05.028.