Expression And Significance Of NGF And Its Receptors In Primary Hepatocellular Carcinoma

ObjectiveThis study is designed to detect the expression level of NGF/NGFR in HCC, para-carcinoma liver and normal liver tissues by immunohistochemistry and investigate the relationship between their expression and the clinical-pathological parameters of HCC. To further understand the mechanism of NGF in HCC, we detected the change of NGF expression in hepatoma cells stimulated by the conditioned medium (CM) of Hepatic stellate cells (HSC).Methods1. Detected the expression of NGF and its recetors in 50 cases of HCC tissues, 23 cases of para-carcinoma liver tissues and 12 cases of nomal liver tissues by immunohistochemistry and their relationship with the clinical-pathological parameters of HCC was analyzed.2. Detected the expression of NGF in different hepatoma cell lines (HepG2, SMMC7721), hepatic stellate cell line (HSC-T6) and normal liver cell line (L02) by immunohistochemistry. We also detected the change of NGF expression in HepG2 cells stimulated under CM of HSC by immunohistochemistry.Results1. Immunohistochemistry in HCC tissues:⑴In HCC tissues, carcinoma cells expressed NGF and TrKA, positive expression was mainly localized in the cytoplasm and membrane of the tumor cells. TrKA was also expressed in the HSCs and fibroblasts of vascular wall in tumor tissue. In para-carcinoma liver tissue, NGF was expressed and TrKA was mainly expressed in hepatic fibrosis and vascular wall. In the normal tissue, they were both negative. p75NTR was weak positive expression in tumor cells and positive in some liver cells in the para-carcinoma tissues and HSC. In the normal liver tissue, p75NTR was strongly expressed.⑵The rate and intensity of NGF/TrKA expression in hepatocellular carcinoma were significantly higher than that in para-carcinoma liver and normal liver tissues. However, the rate and intensity of p75NTR expression in hepatocellular carcinoma were significantly lower than that in para-carcinoma liver and normal liver tissue.⑶The expression of NGF/TrkA was positively correlated with the pathological grade of HCC, and the expression intensity of NGF/TrkA was significantly higher in cases with cancer embolus in portal vein than that in cases without cancer embolus in portal vein. The expression of p75NTR and the pathological grade of HCC was negatively correlated, the expression intensity of p75NTR in group with portal vein tumor thrombus was significantly lower than that in group without portal vein tumor thrombus.2. Immunohistochemistry in cell lines:⑴NGF was expressed in HepG2, SMMC7721 and HSC-T6, the positive particles were mainly distributed in the cytoplasm and membrane, the expression intensity in hepatoma cell lines was significantly higher than that in HSC-T6. In normal liver cell line (L02), NGF was negative.⑵The expression intensity of NGF in HepG2 cells cultured alone was significantly lower than that in HepG2 cells treated by CM of HSC. With the increasing of CM concentration and prolongating of exposed time, the expression intensity of NGF in HepG2 cells was gradually enhanced.ConclusionsThe expression intensity of NGF, TrkA and p75NTR was strongly correlated with the pathological grade, invasion and metastasis of HCC. The NGF expression was significantly increased in HepG2 cells treated by CM of HSC. The result suggested that NGF may affect the growth, invasion and metastasis of HCC through autocrine and paracrine manner, and indicated that NGF/NGFR may play an important role in the progression of HCC.