Department of general surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, PR China.
Department of general surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, PR China.
Matrix Biol. 2024 Sep;132:59-71. doi: 10.1016/j.matbio.2024.06.004. Epub 2024 Jun 25.
Despite advances in surgery, radiotherapy and immunotherapy, the mortality rate for gastric cancer remains one of the highest in the world. A large body of evidence has demonstrated that cancer-associated fibroblasts (CAFs), as core members of the stroma, can secrete cytokines, proteins and exosomes to create a tumour microenvironment that is conducive to cancer cell survival. CAFs can also interact with cancer cells to form a complex signalling network, enabling cancer cells to more easily metastasise to other organs and tissues in the body and develop metastatic foci. In this review, we provide an overview of the CAFs concept and activators. We focus on elucidating their effects on immune cells, intratumoural vasculature, extracellular matrix, as well as cancer cell activity, metastatic power and metabolism, and on enhancing the metastatic ability of cancer cells through activation of JAK/STAT, NF/κB and CXCL12/CXCR4. Various therapeutic agents targeting CAFs are also under development and are expected to improve the prognosis of gastric cancer in combination with existing treatment options.
尽管手术、放疗和免疫疗法取得了进展，但胃癌的死亡率仍然是全球最高的之一。大量证据表明，癌症相关成纤维细胞（CAFs）作为基质的核心成员，可以分泌细胞因子、蛋白质和外泌体，创造有利于癌细胞存活的肿瘤微环境。CAFs 还可以与癌细胞相互作用，形成复杂的信号网络，使癌细胞更容易转移到体内的其他器官和组织，并形成转移灶。在这篇综述中，我们概述了 CAFs 的概念和激活剂。我们重点阐述了它们对免疫细胞、肿瘤内血管、细胞外基质以及癌细胞活性、转移能力和代谢的影响，并通过激活 JAK/STAT、NF/κB 和 CXCL12/CXCR4 来增强癌细胞的转移能力。目前还在开发针对 CAFs 的各种治疗药物，预计将与现有治疗方案结合使用，改善胃癌的预后。
