PMID- 25150213
OWN - NLM
STAT- MEDLINE
DCOM- 20141121
LR  - 20140922
IS  - 1873-2968 (Electronic)
IS  - 0006-2952 (Linking)
VI  - 91
IP  - 4
DP  - 2014 Oct 15
TI  - Brain-derived neurotrophic factor increases vascular endothelial growth factor 
      expression and enhances angiogenesis in human chondrosarcoma cells.
PG  - 522-33
LID - S0006-2952(14)00463-8 [pii]
LID - 10.1016/j.bcp.2014.08.008 [doi]
AB  - Chondrosarcomas are a type of primary malignant bone cancer, with a potent 
      capacity for local invasion and distant metastasis. Brain-derived neurotrophic 
      factor (BDNF) is commonly upregulated during neurogenesis. The aim of the present 
      study was to examine the mechanism involved in BDNF-mediated vascular endothelial 
      growth factor (VEGF) expression and angiogenesis in human chondrosarcoma cells. 
      Here, we knocked down BDNF expression in chondrosarcoma cells and assessed their 
      capacity to control VEGF expression and angiogenesis in vitro and in vivo. We 
      found knockdown of BDNF decreased VEGF expression and abolished chondrosarcoma 
      conditional medium-mediated angiogenesis in vitro as well as angiogenesis effects 
      in vivo in the chick chorioallantoic membrane and Matrigel plug nude mouse 
      models. In addition, in the xenograft tumor angiogenesis model, the knockdown of 
      BDNF significantly reduced tumor growth and tumor-associated angiogenesis. BDNF 
      increased VEGF expression and angiogenesis through the TrkB receptor, PLCgamma, PKCalpha, 
      and the HIF-1alpha signaling pathway. Finally, we analyzed samples from 
      chondrosarcoma patients by immunohistochemical staining. The expression of BDNF 
      and VEGF protein in 56 chondrosarcoma patients was significantly higher than in 
      normal cartilage. In addition, the high level of BDNF expression correlated 
      strongly with VEGF expression and tumor stage. Taken together, our results 
      indicate that BDNF increases VEGF expression and enhances angiogenesis through a 
      signal transduction pathway that involves the TrkB receptor, PLCgamma, PKCalpha, and the 
      HIF-1alpha. Therefore, BDNF may represent a novel target for anti-angiogenic therapy 
      for human chondrosarcoma.
CI  - Copyright (c) 2014 Elsevier Inc. All rights reserved.
FAU - Lin, Chih-Yang
AU  - Lin CY
AD  - Graduate Institute of Basic Medical Science, China Medical University, No. 91, 
      Hsueh-Shih Road, Taichung, Taiwan.
FAU - Hung, Shih-Ya
AU  - Hung SY
AD  - Epigenome Research Center, China Medical University Hospital, Taichung, Taiwan; 
      Graduate Institute of Integrated Medicine, College of Chinese Medicine, China 
      Medical University, Taichung, Taiwan.
FAU - Chen, Hsien-Te
AU  - Chen HT
AD  - School of Chinese Medicine, College of Chinese Medicine, China Medical 
      University, Taichung, Taiwan; Department of Orthopedic Surgery, China Medical 
      University Hospital, Taichung, Taiwan; Department of Materials Science and 
      Engineering, Feng Chia University, Taichung, Taiwan.
FAU - Tsou, Hsi-Kai
AU  - Tsou HK
AD  - Department of Materials Science and Engineering, Feng Chia University, Taichung, 
      Taiwan; Department of Neurosurgery, Taichung Veterans General Hospital, Taichung, 
      Taiwan; Department of Early Childhood Care and Education, Jen-Teh Junior College 
      of Medicine, Nursing and Management, Miaoli County, Taiwan.
FAU - Fong, Yi-Chin
AU  - Fong YC
AD  - School of Chinese Medicine, College of Chinese Medicine, China Medical 
      University, Taichung, Taiwan; Department of Orthopedic Surgery, China Medical 
      University Hospital, Taichung, Taiwan.
FAU - Wang, Shih-Wei
AU  - Wang SW
AD  - Department of Medicine, Mackay Medical College, New Taipei City, Taiwan.
FAU - Tang, Chih-Hsin
AU  - Tang CH
AD  - Graduate Institute of Basic Medical Science, China Medical University, No. 91, 
      Hsueh-Shih Road, Taichung, Taiwan; Department of Pharmacology, School of 
      Medicine, China Medical University, Taichung, Taiwan; Department of 
      Biotechnology, College of Health Science, Asia University, Taichung, Taiwan. 
      Electronic address: chtang@mail.cmu.edu.tw.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140819
PL  - England
TA  - Biochem Pharmacol
JT  - Biochemical pharmacology
JID - 0101032
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - EC 2.7.10.1 (Receptor, trkB)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/genetics/*physiology
MH  - Cell Line, Tumor
MH  - Chondrosarcoma/blood supply/*metabolism
MH  - Gene Knockdown Techniques
MH  - Humans
MH  - Male
MH  - Mice
MH  - Mice, SCID
MH  - *Neovascularization, Pathologic
MH  - Receptor, trkB/physiology
MH  - Vascular Endothelial Growth Factor A/*metabolism
OTO - NOTNLM
OT  - Angiogenesis
OT  - BDNF
OT  - Chondrosarcoma
OT  - TrkB
OT  - VEGF
EDAT- 2014/08/26 06:00
MHDA- 2014/12/15 06:00
CRDT- 2014/08/24 06:00
PHST- 2014/03/18 00:00 [received]
PHST- 2014/08/11 00:00 [revised]
PHST- 2014/08/11 00:00 [accepted]
PHST- 2014/08/24 06:00 [entrez]
PHST- 2014/08/26 06:00 [pubmed]
PHST- 2014/12/15 06:00 [medline]
AID - S0006-2952(14)00463-8 [pii]
AID - 10.1016/j.bcp.2014.08.008 [doi]
PST - ppublish
SO  - Biochem Pharmacol. 2014 Oct 15;91(4):522-33. doi: 10.1016/j.bcp.2014.08.008. Epub 
      2014 Aug 19.