PMID- 28966935
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200930
IS  - 2331-091X (Print)
IS  - 2331-0928 (Electronic)
VI  - 4
IP  - 2
DP  - 2017
TI  - Brain derived neutrophic factor (BDNF) coordinates lympho-vascular metastasis 
      through a fibroblast-governed paracrine axis in the tumor microenvironment.
LID - e1566 [pii]
LID - 10.14800/ccm.1566 [doi]
AB  - It has long been known that the tumor microenvironment contributes to the 
      proliferation and survival of neoplasms through the constant interaction with the 
      stromal and immune compartments. In this investigation, we explored the role of 
      cancer-associated fibroblasts (CAFs) in the regulation of the tumor 
      microenvironment in head and neck squamous cell carcinoma (HNSCC) though a 
      complex intercellular BDNF-TrkB signaling system. Our studies show that 
      conditioned media derived from patient-derived CAFs promoted HNSCC cell 
      proliferation, in vitro cell migration, cell invasion and chemotherapy 
      resistance, compared to normal fibroblasts. Furthermore, examination of the in 
      vivo impact of CAF pathophysiology in the tumor microenvironment in animal 
      xenograft models revealed that HNSCC cell lines in combination with CAFs promoted 
      tumor growth and increased incidence of lymphovascular metastasis as compared to 
      injection of tumor cells or CAF cells alone. Using pharmacological and genetic 
      alterations, we mechanistically demonstrate the critical importance of BDNF-TrkB 
      signaling in the tumor microenvironment. These investigations further support the 
      rationale for BDNF/TRKB targeted therapy against in the treatment of HNSCC.
FAU - Jiffar, Tilahun
AU  - Jiffar T
AD  - Department of Head and Neck Surgery, MD Anderson Cancer Center, Houston TX 77030, 
      USA.
FAU - Yilmaz, Turker
AU  - Yilmaz T
AD  - Department of Head and Neck Surgery, MD Anderson Cancer Center, Houston TX 77030, 
      USA.
FAU - Lee, Junegoo
AU  - Lee J
AD  - Department of Head and Neck Surgery, MD Anderson Cancer Center, Houston TX 77030, 
      USA.
FAU - Miller, Yair
AU  - Miller Y
AD  - Department of Head and Neck Surgery, MD Anderson Cancer Center, Houston TX 77030, 
      USA.
FAU - Feng, Lei
AU  - Feng L
AD  - Department of Biostatistics, MD Anderson Cancer Center, Houston TX 77030, USA.
FAU - El-Naggar, Adel
AU  - El-Naggar A
AD  - Department of Pathology, MD Anderson Cancer Center, Houston TX 77030, USA.
FAU - Kupferman, Michael E
AU  - Kupferman ME
AD  - Department of Head and Neck Surgery, MD Anderson Cancer Center, Houston TX 77030, 
      USA.
LA  - eng
GR  - K08 DE019185/DE/NIDCR NIH HHS/United States
GR  - L30 CA111058/CA/NCI NIH HHS/United States
GR  - P30 CA016672/CA/NCI NIH HHS/United States
PT  - Journal Article
DEP - 20170710
PL  - United States
TA  - Cancer Cell Microenviron
JT  - Cancer cell & microenvironment
JID - 101647794
PMC - PMC5617346
MID - NIHMS894244
COIS- Conflicting interests The authors have declared that no conflict of interests 
      exist.
EDAT- 2017/10/03 06:00
MHDA- 2017/10/03 06:01
PMCR- 2017/09/27
CRDT- 2017/10/03 06:00
PHST- 2017/10/03 06:00 [entrez]
PHST- 2017/10/03 06:00 [pubmed]
PHST- 2017/10/03 06:01 [medline]
PHST- 2017/09/27 00:00 [pmc-release]
AID - e1566 [pii]
AID - 10.14800/ccm.1566 [doi]
PST - ppublish
SO  - Cancer Cell Microenviron. 2017;4(2):e1566. doi: 10.14800/ccm.1566. Epub 2017 Jul 
      10.