Role of the adipokine chemerin in hepatocellular carcinoma

脂肪因子凯莫瑞在肝细胞癌中的作用

基本信息

批准号：
313497054
负责人：
Professorin Dr. Christa Büchler
金额：
--
依托单位：
Klinik und Poliklinik für Innere Medizin I
依托单位国家：
德国
项目类别：
Research Grants
财政年份：
2016
资助国家：
德国
起止时间：
2015-12-31 至 2019-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/313497054?language=en
关键词：
Role adipokine chemerin hepatocellular carcinoma

项目摘要

Chemerin is an attractant for immune cells, it regulates angiogenesis and cell proliferation. Our group has shown that active chemerin (Chem-157) induces cell death of hepatoma cells while the viability of primary hepatocytes is not affected. Chem-157 also reduces tumor weight in a HepG2 xenograft mouse model. Further, in the literature reduced expression of liver chemerin in hepatocellular carcinoma (HCC) is found to be associated with poor prognosis. The chemerin receptor CMKLR1 is increased in HCC tissue compared to adjacent non-tumorous tissues. Object of the current study is to evaluate a possible beneficial effect of adenoassociated virus 8 mediated hepatic overexpression of Chem-157 in the diethylnitrosamine mouse model widely used in HCC research. In-vitro studies are performed to identify the underlying signaling pathways involved in Chem-157 induced cell death in human and murine cells. Non-alcoholic steatohepatitis (NASH) is one of the risk factors for HCC development. Hepatic chemerin is increased in NASH liver suggesting that protective function of this protein is lost during progression to HCC. In a NASH-HCC animal model expression of hepatic chemerin and its receptors will be measured to address this issue. Further, chemerin activity is analyzed in serum of HCC and NASH-HCC models. HCC is a frequent cancer worldwide and treatment options for progressed HCC have not been established yet. Preliminary data from our group suggest that Chem-157 selectively kills hepatoma cells and the current project intends to further corroborate these findings.

Chemerin是免疫细胞的吸引力，它调节血管生成和细胞增殖。我们的小组表明，活性化学蛋白（Chem-157）诱导肝癌细胞的细胞死亡，而原发性肝细胞的生存能力不受影响。 Chem-157还减少了HEPG2异种移植小鼠模型中的肿瘤重量。此外，在文献中，发现肝细胞癌（HCC）中肝化学蛋白的表达降低与预后不良有关。与邻近的非肿瘤组织相比，HCC组织中Chemerin受体CMKLR1增加。当前研究的目的是评估腺体相关病毒8在HCC研究中广泛使用的二乙基硝基胺小鼠模型中Chem-157介导的肝过表达的可能有益作用。进行体外研究以识别Chem-157诱导的人和鼠细胞中涉及的细胞死亡的潜在信号通路。非酒精性脂肪性肝炎（NASH）是HCC发育的危险因素之一。 NASH肝脏中肝化学素的增加，表明该蛋白在进展为HCC期间丧失了该蛋白的保护功能。在NASH-HCC动物模型的表达中，肝化学蛋白及其受体将被测量以解决此问题。此外，在HCC和NASH-HCC模型的血清中分析了化学活性。 HCC是全球频繁的癌症，尚未建立进步的HCC治疗选择。来自我们小组的初步数据表明，Chem-157有选择地杀死肝癌细胞，而当前的项目打算进一步证实这些发现。