TrkB antibody elicits cytotoxicity and suppresses migration/invasion of transitional cell carcinoma cells.
BDNF (brain-derived neurotrophic factor) and its receptor TrkB (tropomyosin receptor kinase B) play important roles in the progression of cancer, including transitional cell carcinoma (TCC) cells reported in our previous investigation. In this study, we used a specific TrkB antibody (Ab) to evaluate its effects on survival, proliferation and migration/invasion in three TCC cell lines (BFTC905, T24 and TSGH8301) in vitro. The TrkB Ab at 1 and 3 microg/ml, but not the TrkA or TrkC Abs, significantly elicited cytotoxicity in TCC cells. The TrkB Ab at 3 microg/ml also induced apoptosis of TCC cells, which may result from up-regulation of phospho-p38 plus down-regulation of survivin and securin expression. The TrkB Ab at 0.5 microg/ml, which did not show cytotoxicity, suppressed migration of TCC cells and invasion of BFTC905 cells, possibly mediated through increased E-cadherin, decreased BDNF-stimulated phospho-PLCgamma1 and reduced MMP-9 activity. These results indicate that TrkB blockade may be a new strategy for TCC therapy.
Huang
Yen Ta
YT
Institute of Pharmacology and Toxicology, Tzu Chi University, Hualien, Taiwan, ROC.
Lai
Pei Chun
PC
Wu
Chia Chen
CC
Cheng
Chuan Chu
CC
Chiu
Ted H
TH
D000906:Antibodies / Q000494:pharmacology*; D015703:Antigens, CD; D017209:Apoptosis / Q000187:drug effects; D015820:Cadherins / Q000378:metabolism; D002295:Carcinoma, Transitional Cell / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000378:metabolism; D051966:Phospholipase C gamma / Q000378:metabolism; D010766:Phosphorylation; D020813:Receptor, trkB / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism; D064249:Securin; D000077022:Survivin; D013997:Time Factors; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D000906:Antibodies; D015703:Antigens, CD; C107489:BIRC5 protein, human; C513384:CDH1 protein, human; D015820:Cadherins; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D064249:Securin; D000077022:Survivin; C578002:pituitary tumor-transforming protein 1, human; D020813:Receptor, trkB; D048051:p38 Mitogen-Activated Protein Kinases; C522157:PLCG1 protein, human; D051966:Phospholipase C gamma; D020780:Matrix Metalloproteinase 9