Maintenance of stemness is associated with the interation of LRP6 and heparin-binding protein CCN2 autocrined by hepatocellular carcinoma.
Maintenance of stemness is associated with the interation of LRP6 and heparin-binding protein CCN2 autocrined by hepatocellular carcinoma.
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干性的维持与肝细胞癌自分泌的 LRP6 和肝素结合蛋白 CCN2 的相互作用有关
DOI：
10.1186/s13046-017-0576-3
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发表时间：
2017-09-04
期刊：
影响因子：
--
通讯作者：
Liu Q
中科院分区：
文献类型：
--
作者：
Jia Q;Bu Y;Wang Z;Chen B;Zhang Q;Yu S;Liu Q
背景肝细胞癌（HCC）化疗的总体疗效较差。在我们前期的研究中发现，奥沙利铂耐药的HCC表现出干细胞性增强，CCN 2和LRP 6水平升高，但CCN 2和LRP 6在HCC患者预后中的作用以及CCN 2和LRP 6之间的相互作用调节机制尚不清楚。并对CCN 2和LRP 6进行了体外和体内功能分析。结果肝癌组织中CCN 2和LRP 6均过表达，且CCN 2和LRP 6水平与肝癌恶性表型和预后均呈正相关。LRP 6可显著上调CCN 2的表达。同时，CCN 2通过与LRP 6结合，以剂量依赖的方式增强肝癌细胞的恶性表型; LRP 6表达下调、HSPGs干扰、CCN 2与LMWH共孵育可显著阻断CCN 2与LRP 6的粘附。结论CCN 2可能通过激活LRP 6，以HSP Gs依赖的方式促进HCC的进展。肝素联合化疗具有协同作用，可能是CCN 2高表达的HCC的治疗选择。
BackgroundThe 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.MethodsThe 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.ResultsCCN2 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.ConclusionsCCN2 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.
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影响因子：
1
作者：
Altinbas, M.;Dikilitas, M.;Coskun, H. S.
通讯作者：
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