Interstitialcells of liver cancer influence the biological function of malignant through the HGF/cMET system / 西安交通大学学报(医学版)

ABSTRACT

Objective To explore the effects of interstitial cells of liver cancer and normal liver cells co‐cultured on the biological function of liver cancer malignancy so as to understand the signal pathway involved by the interaction between these cells and confirm the role of interstitial cells in cancer progression in tumor microenvironment .Methods We co‐cultured interstitial cells or hepatocyte growth factor (HGF ) and human normal liver cell L‐02 ,and then detected the expressions of the tumor‐suppressing gene PTEN and the oncogene K‐RAS and changes of cell proliferation .The downstream signaling pathways were detected by Real‐time PCR and Western blot .Results The expression of PTEN was downregulated at the transcription level by 1 .15 times and translation level by 10 times (P<0 .05) ,while the transcription level and translation level of K‐RAS increased by 1 .4 times and more than 9 times , respectively ( P< 0 .05 ) in normal liver cells co‐cultured with liver cancer mesenchymal cells .The proliferation ability was increased by more than 2 times .ELISA experiment results showed that the medium from co‐culture contained HGF over 3 times more than the control group ( P<0 .05 ,1 085+108 vs .387+23) .At the same time ,cells in the experimental group expressed more than four times of cMET than the control group cells (P< 0 .05) .Exogenous HGF consistently promoted liver cell proliferation and viability (P<0 .05) .Conclusion Our study shows that liver cancer interstitial cells activate the HGF/cMET signaling pathway by secreting HGF and promote the proliferation of normal liver cells ,suggesting a new way to explore the molecular mechanism of tumor microenvironment in tumor development and treatment of hepatocellular carcinoma .