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Tenascin-C expression is associated with poor prognosis in hepatocellular carcinoma (HCC) patients and the inflammatory cytokine TNF-?-induced TNC expression promotes migration in HCC cells.

ABSTRACT: Although tenascin-c (TNC) in inflammatory microenvironment contributes to progression in some tumors, its role in hepatocellular carcinoma (HCC) in metastasis and the mechanism by which TNC expression is regulated in HCC cells are elusive. In this study, we examined TNC expression in 100 HCC tissue samples by immunohistochemistry and compared which between the groups with or without metastasis. TNC expression was higher in metastatic HCC tissues than that in the non-metastatic HCC tissues, which was associated with the Knodell inflammation scores. Importantly, high level of TNC expression was associated with lower survival rate and shorter survival time in the HCC patients. We then investigated the mechanism by which TNC expression is regulated in HCC cells with an in vitro cell culture system. The recombinant TNF-? and conditioned medium from macrophages induced TNC expression at both mRNA and protein levels in HepG2 cells. The induction of TNC expression by conditioned medium from macrophages was suppressed by a TNF-? neutralizing antibody. TNF-?-promoted cell migration was inhibited by a TNC siRNA. In addition, TNF-?-induced TNC expression was blocked by a NF-?B pathway inhibitor. These results suggest that TNF-? in the tumor microenvironment induces TNC expression in HCC cells through the NF-?B pathway, which in turn, promotes HCC cell migration. Thus, TNC may play an important role in promoting HCC metastasis and TNC expression could be a predictive factor for poor prognosis in HCC patients.

SUBMITTER: Nong Y

PROVIDER: S-EPMC4396033 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Tenascin-C expression is associated with poor prognosis in hepatocellular carcinoma (HCC) patients and the inflammatory cytokine TNF-α-induced TNC expression promotes migration in HCC cells.

Nong Yunhong Y Wu Dongbo D Lin Yong Y Zhang Yongqiang Y Bai Lang L Tang Hong H

American journal of cancer research 20150115 2

Although tenascin-c (TNC) in inflammatory microenvironment contributes to progression in some tumors, its role in hepatocellular carcinoma (HCC) in metastasis and the mechanism by which TNC expression is regulated in HCC cells are elusive. In this study, we examined TNC expression in 100 HCC tissue samples by immunohistochemistry and compared which between the groups with or without metastasis. TNC expression was higher in metastatic HCC tissues than that in the non-metastatic HCC tissues, which ...[more]

PMID: 25973315

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Project description:BACKGROUND:ZW10 interactor was recently reported to correlate with human cancers. However, the prognostic value of ZW10 interactor in hepatocellular carcinoma was not reported. METHODS:The expression level of ZW10 interactor was evaluated by Western blot and immunohistochemistry using tissue microarray. In the present study, we used 5 pairs of hepatocellular carcinoma and peritumoral frozen tissues for Western blot, and 70 paired paraffin-embedded hepatocellular carcinoma and peritumoral tissues as expression pattern cohort (cohort 1), and 280 paraffin-embedded hepatocellular carcinoma tissues were used as prognostic cohort (cohort 2). The integral optic density representing the expression level of ZW10 interactor in each tissue sample, was calculated using Image-Pro Plus. The integral optic density was added to the X-tile software for calculating the outcome-based cut point. Kaplan-Meier and Cox regression were used to evaluate the prognostic values. RESULTS:The expression level ZW10 interactor was decreased in hepatocellular carcinoma tissues in 85.7% (60/70) of the cases compared to the corresponding peritumoral tissues evaluated by immunohistochemistry. Similar result was obtained by Western blot analysis using frozen tissue. Expression of ZW10 interactor was closely correlated with age ( P = .0001) and liver cirrhosis in cohort 1 and tumor node metastasis ( P = .018), tumor size ( P = .005), and vascular invasion ( P = .022) in cohort 2 based on ?2 analyses. Survival analyses indicated that patients with hepatocellular carcinoma having low ZW10 interactor expression had a shorter overall survival time and time to recurrence compared to cases with high ZW10 interactor expression in the prognostic cohort ( P < .0001 for both overall survival and time to recurrence ). Univariate and multivariate Cox analyses indicated that ZW10 interactor was an independent prognostic factor for overall survival ( P = .033). CONCLUSIONS:The present study clearly showed that ZW10 interactor was frequently decreased in hepatocellular carcinoma compared to nontumoral liver tissues, and ZW10 interactor could serve as a potential prognostic marker in patients with hepatocellular carcinoma after surgery.

Dataset Information

Tenascin-C expression is associated with poor prognosis in hepatocellular carcinoma (HCC) patients and the inflammatory cytokine TNF-?-induced TNC expression promotes migration in HCC cells.

Publications

Tenascin-C expression is associated with poor prognosis in hepatocellular carcinoma (HCC) patients and the inflammatory cytokine TNF-α-induced TNC expression promotes migration in HCC cells.

Similar Datasets

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