Role of hepatic stellate cells in the selection and adaptation of metastasizing cancer cells inthe hepatic environment

肝星状细胞在肝脏环境中转移癌细胞的选择和适应中的作用

• 批准号: 257889219
• 负责人: Professor Dr. Claus Hellerbrand
• 金额: --
• 依托单位: Institut für Biochemie
• 依托单位国家: 德国
• 项目类别: Research Units
• 财政年份: 2014
• 资助国家: 德国
• 起止时间: 2013-12-31 至 2021-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/257889219?language=en
• 关键词: Role; hepatic; stellate; cells; selection

Within the first funding period, we have increased the body of evidence regarding the important role of hepatic stellate cells (HSCs) in liver metastasis. Particularly, we found that HGF (hepatocyte growth factor) is a central mediator of HSZ-mediated cancer cell activation. Moreover, we identified mTORC2 (mammalian Target of Rapamycin Complex 2) as a crucial signaling pathway in HSC/cancer cell interaction. In addition, preliminary data indicate that several key features of liver metastasis, such as motility and metabolism are critically affected by the HSC-cancer cell/mTORC2 axis. Therefore, our focus is the bidirectional interaction of HSCs with cancer cells upon modulation of mTORC2.Within the consortium we want to get a deeper insight into the regulatory mechanisms and the functional role of HSCs on the selection and adaptation of metastasizing cancer cells. Besides the direct HSC-cancer cell interaction, we will assess effects on the local microenvironment. Furthermore, experimental and therapeutic strategies for mTORC2 blockade will be assessed in different models. The modulation of the HSC-cancer cell interaction may prove to be effective in reducing liver metastasis and providing a survival benefit for patients by targeting both, cancer cells and the tumor microenvironment.

在第一个资助期内，我们增加了关于肝星状细胞（HSC）在肝转移中重要作用的证据。特别地，我们发现HGF（肝细胞生长因子）是HSZ介导的癌细胞活化的中心介质。此外，我们确定mTORC 2（哺乳动物雷帕霉素复合物靶蛋白2）是HSC/癌细胞相互作用中的关键信号通路。此外，初步数据表明，肝转移的几个关键特征，如运动和代谢受到HSC-癌细胞/mTORC 2轴的严重影响。因此，本研究的重点是探讨mTORC 2调控下HSC与癌细胞的双向相互作用，以期更深入地了解HSC在转移癌细胞选择和适应中的调控机制和功能作用。除了直接的HSC-癌细胞相互作用外，我们还将评估对局部微环境的影响。此外，将在不同模型中评估mTORC 2阻断的实验和治疗策略。HSC-癌细胞相互作用的调节可以证明有效地减少肝转移，并通过靶向癌细胞和肿瘤微环境为患者提供生存益处。