Hepatoma-derived growth factor promotes growth and metastasis of hepatocellular carcinoma cells.
We aimed to elucidate the effects of hepatoma-derived growth factor (HDGF) on growth and metastasis of hepatocellular carcinoma (HCC) cells. Tissue microarrays with 236 HCC specimens and 18 extrahepatic metastases were utilized to detect the HDGF expression by immunohistochemistry. Meanwhile, HDGF expressions in HCC cell lines with different metastatic potentials were examined using immunofluorescence staining, real-time PCR and western blotting. After HDGF silencing, the growth and metastatic potentials of HCC cells were evaluated by soft agar assay, invasion assay, together with tumorigenicity assay in nude mice. The gelatin zymography was performed by detecting MMP-2 and MMP-9 levels. Additionally, western blotting was conducted to determine the levels of total and phosphorylated ERK1/2, JNK, p38 and Akt. The results showed that HDGF was overexpressed in HCC metastasis tumour, and the expression increased with the differentiation degree of tumours (Grade I 44.0%, Grade II 48.4% and Grade III 65.6%). Consistently, HDGF levels were positively associated with the metastatic capability of HCC cells (MHCC97L < MHCC97H < HCCLM3). The growth and metastasis were suppressed by HDGF-siRNA. Gelatinolytic activities were enhanced in the three metastatic HCC cell lines, but had no significant difference among them. The tumourigenicity and metastatic capability of HCCLM3 cells in nude mice were inhibited after silencing HDGF. Meanwhile, HDGF-siRNA specifically suppressed the total and phosphorylated protein levels of ERK1/2, while not JNK, p38 and Akt. In conclusion, HDGF was overexpressed in HCC patients and cells, and HDGF might be closely correlated with HCC metastasis via regulating ERK signalling pathway. Copyright © 2016 John Wiley & Sons, Ltd.
Department of Hepatobiliary Surgery, PLA General Hospital and Institute of Hepatobiliary of Chinese PLA, Beijing, China.
Guang-Yun
GY
Yang
Department of Hepatobiliary Surgery, PLA General Hospital and Institute of Hepatobiliary of Chinese PLA, Beijing, China.
Ai-Qun
AQ
Zhang
Department of Hepatobiliary Surgery, PLA General Hospital and Institute of Hepatobiliary of Chinese PLA, Beijing, China.
Jing
J
Wang
Department of Hepatobiliary Surgery, PLA General Hospital and Institute of Hepatobiliary of Chinese PLA, Beijing, China.
Chong-Hui
CH
Li
Department of Hepatobiliary Surgery, PLA General Hospital and Institute of Hepatobiliary of Chinese PLA, Beijing, China.
Xian-Qiang
XQ
Wang
Department of Hepatobiliary Surgery, PLA General Hospital and Institute of Hepatobiliary of Chinese PLA, Beijing, China.
Ke
K
Pan
Department of Hepatobiliary Surgery, PLA General Hospital and Institute of Hepatobiliary of Chinese PLA, Beijing, China.
Cheng
C
Zhou
Department of Hepatobiliary Surgery, PLA General Hospital and Institute of Hepatobiliary of Chinese PLA, Beijing, China.
Jia-Hong
JH
Dong
D000328:Adult; D000818:Animals; D063646:Carcinogenesis / Q000473:pathology; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008113:Liver Neoplasms / Q000235:genetics / Q000473:pathology*; D008297:Male; D008819:Mice, Nude; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010766:Phosphorylation; D034741:RNA, Small Interfering / Q000378:metabolism; D046888:Tissue Array Analysis
D036341:Intercellular Signaling Peptides and Proteins; D034741:RNA, Small Interfering; C051610:hepatoma-derived growth factor; D048049:Extracellular Signal-Regulated MAP Kinases
ERK signalling pathway; growth; hepatocellular carcinoma; hepatoma-derived growth factor; metastasis