Abstract
BackgroundHepatectomy generally offers the best chance of long-term survival for patients with hepatocellular carcinoma (HCC). Many studies have shown that hepatectomy accelerates tumor metastasis, but the mechanism remains unclear.MethodsAn orthotopic nude mice model with palliative HCC hepatectomy was performed in this study. Metastasis-related genes in tumor following resection were screened; HCC invasion, metastasis, and some molecular alterations were examined in vivo and in vitro. Clinical significance of key gene mRNA expression was also analyzed.ResultsMetastasis suppressor 1 (MTSS1) located in the central position of gene function net of residual HCC. MTSS1 was up-regulated in residual tumor after palliative resection. In hepatitis B-related HCC patients undergone palliative hepatectomy, those with higher MTSS1 mRNA expression accompanied by activation of matrix metalloproteinase 2 (MMP2) in residual HCC, had earlier residual HCC detection after hepatectomy and poorer survival when compared to those with lower MTSS1. In different cell lines, the levels of MTSS1 mRNA increased in parallel with metastatic potential. MTSS1 down regulation via siRNA decreased MMP2 activity, reduced invasive potentials of HCC by 28.9 % in vitro, and averted the deteriorated lung metastatic extent in vivo.ConclusionsThe poor prognosis of hepatitis B-related HCC patients following palliative hepatectomy associates with elevated MTSS1 mRNA expression; therefore, MTSS1 may provide a new research field for HCC diagnosis and treatment.Electronic supplementary materialThe online version of this article (doi:10.1186/s13046-016-0361-8) contains supplementary material, which is available to authorized users.
Highlights
Hepatectomy generally offers the best chance of long-term survival for patients with hepatocellular carcinoma (HCC)
The current study provides the first evidence that elevated metastasis suppressor 1 (MTSS1) mRNA expression exacerbates lung metastasis after palliative resection in an HCC model, with poor prognosis of hepatitis B-related patients with HCC treated with palliative hepatectomy
In vitro invasion assay The MHCC97H cells (5 × 104 cells/well) treated with MTSS1 small interfering RNA (siRNA) lentivirus, empty lentivirus or with control were added to the upper chamber (100 μL DMEM), and 600 μL conditioned medium was added to the lower chamber
Summary
Hepatectomy generally offers the best chance of long-term survival for patients with hepatocellular carcinoma (HCC). Huang et al Journal of Experimental & Clinical Cancer Research (2016) 35:85 hepatic resection exacerbates tumor growth and triggers tumor metastasis [5,6,7]. We found that palliative resection enhances the metastatic potential of residual HCC [5]. This study employed an orthotopic human HCC model with high metastatic potential in nude mice. This model was developed at Liver Cancer Institute, Fudan University [5, 8]. Using Human Tumor Metastasis Microarray, we screened the metastasis-related genes in tumor tissues following palliative resection, and found that up-regulated metastasis suppressor 1 (MTSS1) was located in the central position of gene function net of residual HCC in liver
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