title: Platelet activation during tumor development, the potential role of BDNF-TrkB autocrine loop.
abstract: Platelets are an important place for the storage of angiogenic factors, such as vascular endothelial growth factor (VEGF) and brain-derived neurotrophic factor (BDNF). The present study aims to investigate the interaction between BDNF-TrkB pathway and platelet activation during tumor development. In an orthotopic hepatocellular carcinoma (HCC) model, increased levels of serum and plasma BDNF were detected with tumor progression. Higher numbers of CD62P+ and TrkB+ platelets were found in the tumor-bearing rats. In the in vitro setting, tumor-conditioned-medium (TCM) and BDNF recombinant protein stimulated CD62P upregulation and subsequent BDNF release in the freshly isolated platelets, whereas this effect could be inhibited by TrkB blockade. TCM and BDNF culture augmented the expression of heat shock protein 90 (Hsp90) in the platelets, which could be reversed by TrkB blockade. In conclusion, this study suggested the presence of BDNF-TrkB autocrine loop in platelets and its importance in regulating platelet activation during tumor development.
authors.affiliation: Centre for the Study of Liver Disease, Department of Surgery, The University of Hong Kong, Pokfulam, Hong Kong, China. zfyang@hkucc.hku.hk
authors.forename: Zhen Fan
authors.initials: ZF
authors.lastname: Yang
authors.forename: David W
authors.initials: DW
authors.lastname: Ho
authors.forename: Chi Keung
authors.initials: CK
authors.lastname: Lau
authors.forename: Ka Ho
authors.initials: KH
authors.lastname: Tam
authors.forename: Chi Tat
authors.initials: CT
authors.lastname: Lam
authors.forename: Ronnie T P
authors.initials: RT
authors.lastname: Poon
authors.forename: Sheung Tat
authors.initials: ST
authors.lastname: Fan
mesh_terms: D000818:Animals; D019898:Autocrine Communication; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D045744:Cell Line, Tumor; D002469:Cell Separation; D008297:Male; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology*; D015539:Platelet Activation; D011485:Protein Binding; D051381:Rats; D011915:Rats, Inbred BUF; D020813:Receptor, trkB / Q000378:metabolism*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D020813:Receptor, trkB