Dataset Information

Maintenance of stemness is associated with the interation of LRP6 and heparin-binding protein CCN2 autocrined by hepatocellular carcinoma.

ABSTRACT:

Background

The overall response rate of hepatocellular carcinoma (HCC) to chemotherapy is poor. In our previous study, oxaliplatin-resistant HCC is found to exhibit an enhanced stemness, and increased levels of CCN2 and LRP6, while the role of CCN2 and LRP6 in the prognosis of HCC patients, and the interaction regulation mechanism between CCN2 and LRP6 are still unclear.

Methods

The expression levels of CCN2 and LRP6 were detected in large cohorts of HCCs, and functional analyses of CCN2 and LRP6 were performed both in vitro and in vivo. The roles of cell surface heparin sulfate proteoglycans (HSPGs) in the mutual regulatory between CCN2 and LRP6 were verified in HCC, and the interventions of low molecular weight heparin sodium (LMWH) were explored.

Results

CCN2 and LRP6 were overexpressed in HCCs, and the CCN2 and LRP6 levels were positively associated with the malignant phenotypes and poor prognosis of HCCs. LRP6 could significantly upregulate the expression of CCN2. Meanwhile, CCN2 was able to enhance malignant phenotype of HCC cells in a dose-dependent manner through binding with LRP6; and knock-down of LRP6 expression, perturbation of HSPGs, co-incubation of CCN2 with LMWH could significantly block the adhesion of CCN2 to LRP6. LMWH enhanced the therapeutic effect of oxaliplatin on HCC with a high CCN2 expression.

Conclusions

CCN2 plays a promoting role in HCC progression through activating LRP6 in a HSPGs-dependent manner. Heparin in combination with chemotherapy has a synergic effect and could be a treatment choice for HCCs with a high CCN2 expression.

SUBMITTER: Jia Q

PROVIDER: S-EPMC5584530 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Publications

Maintenance of stemness is associated with the interation of LRP6 and heparin-binding protein CCN2 autocrined by hepatocellular carcinoma.

Jia Qingan Q Bu Yang Y Wang Zhiming Z Chen Bendong B Zhang Qiangbo Q Yu Songning S Liu Qingguang Q

Journal of experimental & clinical cancer research : CR 20170904 1

<h4>Background</h4>The overall response rate of hepatocellular carcinoma (HCC) to chemotherapy is poor. In our previous study, oxaliplatin-resistant HCC is found to exhibit an enhanced stemness, and increased levels of CCN2 and LRP6, while the role of CCN2 and LRP6 in the prognosis of HCC patients, and the interaction regulation mechanism between CCN2 and LRP6 are still unclear.<h4>Methods</h4>The expression levels of CCN2 and LRP6 were detected in large cohorts of HCCs, and functional analyses ...[more]

PMID: 28870205

Similar Datasets

Project description:BackgroundEvidence suggests that many types of cancers are composed of different cell types, including cancer stem cells (CSCs). We have previously shown that the chemotherapeutic agent oxaliplatin induced epithelial-mesenchymal transition, which is thought to be an important mechanism for generating CSCs. In the present study, we investigate whether oxaliplatin-treated cancer tissues possess characteristics of CSCs, and explore oxaliplatin resistance in these tissues.MethodsHepatocellular carcinoma cells (MHCC97H cells) were subcutaneously injected into mice to form tumors, and the mice were intravenously treated with either oxaliplatin or glucose. Five weeks later, the tumors were orthotopically xenografted into livers of other mice, and these mice were treated with either oxaliplatin or glucose. Metastatic potential, sensitivity to oxaliplatin, and expression of CSC-related markers in the xenografted tumor tissues were evaluated. DNA microarrays were used to measure changes in gene expression as a result of oxaliplatin treatment. Additionally, an oxaliplatin-resistant cell line (MHCC97H-OXA) was established to assess insulin-like growth factor 1 secretion, cell invasion, cell colony formation, oxaliplatin sensitivity, and expression of CSC-related markers. The effects of an insulin-like growth factor 1 receptor inhibitor were also assessed.ResultsOxaliplatin treatment inhibited subcutaneous tumor growth. Tumors from oxaliplatin-treated mice that were subsequently xenografted into livers of other mice exhibited that decreasing sensitivity to oxaliplatin and increasing pulmonary metastatic potential. Among the expression of CSC-related proteins, the gene for insulin-like growth factor 1, was up-regulated expecially in these tumor tissues. Additionally, MHCC97H-OXA cells demonstrated that increasing cell invasion, colony formation, and expression of insulin-like growth factor 1 and CSC-related markers, whereas treatment with an inhibitor of the insulin-like growth factor 1 receptor suppressed these effects.ConclusionMaintenance of stemness in oxaliplatin-resistant hepatocellular carcinoma cells is associated with increased autocrine of IGF1.

Dataset Information

Maintenance of stemness is associated with the interation of LRP6 and heparin-binding protein CCN2 autocrined by hepatocellular carcinoma.

Background

Methods

Results

Conclusions

Publications

Maintenance of stemness is associated with the interation of LRP6 and heparin-binding protein CCN2 autocrined by hepatocellular carcinoma.

Similar Datasets

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