Jia Wentao, Liang Shufang, Cheng Binbin, Ling Changquan
School of Traditional Chinese Medicine, Naval Medical University, Shanghai, China.
Department of Traditional Chinese Medicine, Changhai Hospital, Navy Medical University, Shanghai, China.
Front Oncol. 2021 Nov 18;11:763519. doi: 10.3389/fonc.2021.763519. eCollection 2021.
Invasion and metastasis are the main reasons for the high mortality of liver cancer, which involve the interaction of tumor stromal cells and malignant cells. Cancer-associated fibroblasts (CAFs) are one of the major constituents of tumor stromal cells affecting tumor growth, invasion, and metastasis. The heterogeneous properties and sources of CAFs make both tumor-supporting and tumor-suppression effects possible. The mechanisms for CAFs in supporting hepatocellular carcinoma (HCC) progression can be categorized into upregulated aggressiveness and stemness, transformed metabolism toward glycolysis and glutamine reductive carboxylation, polarized tumor immunity toward immune escape of HCC cells, and increased angiogenesis. The tumor-suppressive effect of fibroblasts highlights the functional heterogenicity of CAF populations and provides new insights into tumor-stromal interplay mechanisms. In this review, we introduced several key inflammatory signaling pathways in the transformation of CAFs from normal stromal cells and the heterogeneous biofunctions of activated CAFs. In view of the pleiotropic regulation properties of traditional Chinese medicine (TCM) and heterogeneous effects of CAFs, we also introduced the application and values of TCM in the treatment of HCC through targeting CAFs.
侵袭和转移是肝癌死亡率高的主要原因，这涉及肿瘤基质细胞与恶性细胞的相互作用。癌症相关成纤维细胞（CAFs）是影响肿瘤生长、侵袭和转移的肿瘤基质细胞的主要成分之一。CAFs的异质性特性和来源使得其既可能产生肿瘤支持作用，也可能产生肿瘤抑制作用。CAFs支持肝细胞癌（HCC）进展的机制可分为上调侵袭性和干性、向糖酵解和谷氨酰胺还原羧化转变代谢、使肿瘤免疫向HCC细胞免疫逃逸极化以及增加血管生成。成纤维细胞的肿瘤抑制作用突出了CAF群体的功能异质性，并为肿瘤-基质相互作用机制提供了新的见解。在本综述中，我们介绍了正常基质细胞转化为CAFs过程中的几个关键炎症信号通路以及活化CAFs的异质生物功能。鉴于中药的多效调节特性和CAFs的异质作用，我们还介绍了中药通过靶向CAFs治疗HCC的应用和价值。
