Interplay between brain-derived neurotrophic factor (BDNF) and platelets in hepatocellular carcinoma (HCC)

Abstract

The present study aims to investigate the significance of serum brain-derived neurotrophic factor (BDNF) in relation to clinicopathological features of hepatocellular carcinoma (HCC) patients undergoing hepatic resection, and to investigate the potential interaction between BDNF and platelets in tumor development in a rat HCC model. Localization of BDNF expression in tissues was performed by immunohistochemistry. Serum levels of BDNF were measured by enzyme-linked immunosorbent assay (ELISA). In the rat HCC model, serum samples were also serially collected during tumor development to measure BDNF levels. In an in vitro setting, primarily isolated platelets were stimulated with different culture media, and the expression of CD62P and tyrosine protein kinase receptor B (TrkB) was determined by flow cytometry. BDNF was expressed in cytoplasm of the tumor cells. Highest levels of serum BDNF and serum BDNF/platelet ratio were detected in the HCC patients. Serum levels of BDNF were positively correlated with platelet count in the HCC patients. A higher level of serum BDNF was significantly correlated with tumor size larger than 5 cm, poorly differentiated HCC, presence of microsatellite, and absence of cirrhosis in the non-tumorous tissues. In rat, serum BDNF levels presented with an increasing trend during tumor development, and a higher number of CD62P+ and TrkB+ platelets were detected in the tumor bearing rats. HCC tumor-conditioned-medium induced an increased expression of CD62P and TrkB on platelets, and stimulated a higher level of BDNF release from the primarily cultured platelets. In conclusion, our data suggested that tumor cell was a source of serum BDNF in both clinical and animal settings. A higher serum BDNF level was associated with more advanced tumor status in HCC patients undergoing hepatic resection. BDNF could stimulate platelet activation through an autocrine mechanism.