The impact of the CXC chemokine CXCL13 mediated B lymphocyte recruitment on the development and progression of hepatocellular carcinoma

CXC趋化因子CXCL13介导的B淋巴细胞募集对肝细胞癌发生发展的影响

• 批准号: 203698703
• 负责人: Professorin Dr. Marie-Luise Berres
• 金额: --
• 依托单位: Klinik für Gastroenterologie, Stoffwechselerkrankungen und Internistische Intensivmedizin (Med. Klinik III)
• 依托单位国家: 德国
• 项目类别: Research Fellowships
• 财政年份: 2011
• 资助国家: 德国
• 起止时间: 2010-12-31 至 2012-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/203698703?language=en
• 关键词: impact; CXC; chemokine; CXCL13; mediated

The hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide associated with a very poor prognosis with an overall survival rate of 3-5%. Most of the HCC develop on the background of pre-existing chronic liver diseases, e.g. chronic hepatitis B or C virus infections and non-alcoholic steatohepatitis, which are histopathologically characterized by a chronic intrahepatic inflammation. During this inflammation, the recruitment of inflammatory cells to the liver is mainly orchestrated by small, soluble molecules which are termed chemokines. Together with their specific receptors they form a very complex system within the liver mediating not only the infiltration and homing of intrahepatic leucocytes but also exhibiting direct modulatory effects on liver resident cells. Recently, it could be demonstrated that the expression of the CXC chemokine CXCL13 is significantly upregulated in the tissue of hepatocellular carcinoma compared to normal or preneoplastic liver samples. CXCL13, which binds to its specific receptor CXCR5, is known to be a selective and highly efficacious chemoattractant for B lymphocytes, a cell population which is enhanced in HCC lesions, and has been shown to exert direct stimulatory effects on various carcinoma cells. However, little is known about its role during chronic liver disease and especially during hepatic carcinogenesis. Therefore, the aim of this project is to identify and characterize the impact of an enhanced CXCL13 expression and the consecutive recruitment of B lymphocytes to the liver on the development and progression of hepatocellular carcinoma. These results should provide a new insight in the molecular mechanisms of hepatic carcinogenesis which could help to facilitate early diagnosis and identify new therapeutic targets in order to improve the prognosis of patients with HCC.

肝细胞癌 (HCC) 是全球第五大常见癌症，预后极差，总生存率为 3-5%。大多数 HCC 是在已有慢性肝病的背景下发生的，例如肝脏疾病。慢性乙型或丙型肝炎病毒感染和非酒精性脂肪性肝炎，其组织病理学特征为慢性肝内炎症。在这种炎症过程中，炎症细胞向肝脏的募集主要是由称为趋化因子的可溶性小分子协调的。它们与它们的特异性受体一起在肝脏内形成一个非常复杂的系统，不仅介导肝内白细胞的浸润和归巢，而且还对肝脏驻留细胞表现出直接调节作用。最近，可以证明，与正常或癌前肝脏样本相比，肝细胞癌组织中CXC趋化因子CXCL13的表达显着上调。 CXCL13与其特异性受体CXCR5结合，被认为是B淋巴细胞的选择性且高效的化学引诱剂，B淋巴细胞是在HCC病变中增强的细胞群，并且已被证明对各种癌细胞发挥直接刺激作用。然而，人们对其在慢性肝病尤其是肝癌发生过程中的作用知之甚少。因此，该项目的目的是确定和表征增强的 CXCL13 表达以及 B 淋巴细胞连续募集至肝脏对肝细胞癌发生和进展的影响。这些结果将为肝癌发生的分子机制提供新的见解，有助于促进早期诊断并确定新的治疗靶点，从而改善肝癌患者的预后。