Hepatoma‐derived growth factor promotes growth and metastasis of hepatocellular carcinoma cells

Abstract

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.

Hepatoma-Derived Growth Factor: An Overview and Its Role as a Potential Therapeutic Target Molecule for Digestive Malignancies

“…HDGF is suggested to be related to lipogenesis, and the change in the lipid metabolism may contribute to the mitosis of hepatoma cells. [2,3,16,19,[32][33][34][35][36][37] Pancreatic cancer…”

“…As HDGF was originally identified as a growth factor for hepatoma cells, various studies have demonstrated that HDGF is associated with the progression of HCC [32][33][34][35][36][37]. The expression of HDGF was detected in several hepatoma-derived cell lines [2,3].…”

“…The expression of HDGF was detected in several hepatoma-derived cell lines [2,3]. In addition, HDGF significantly increases the proliferation of hepatoma cells [16,36]. Moreover, HDGF was found to be associated with tumor growth in a xenograft model in vivo [19].…”

“…Moreover, the expression of HDGF is strongly associated with the clinical course of HCC after surgery, and higher HDGF expression levels were found to be related to a poorer prognosis [34]. In fact, various independent groups have demonstrated that HCC patients with higher HDGF expression levels showed an unfavorable clinical outcome in comparison to those with lower HDGF expression levels [33][34][35][36][37], and the expression of HDGF was found to be independently associated with disease-free and overall survival after curative surgery in HCC patients. Accumulated findings suggest that HDGF has a significant clinical role in the disease progression of human HCC.…”

Cell-Specific PEAR1 Methylation Studies Reveal a Locus that Coordinates Expression of Multiple Genes

“…Two other chromosome contacts with PEAR1 involve two genes whose abnormal expression is reported to lead to growth of several tumours [ 66 , 67 , 68 , 69 , 70 ]. PRCC is involved in mRNA splicing and reported to have a role in cell cycle delay.…”