The University of Queensland Diamantina Institute, The University of Queensland, Woolloongabba, QLD, Australia.
Gallipoli Medical Research Institute, Greenslopes Private Hospital, Brisbane, QLD, Australia.
Int J Cancer. 2020 Sep 15;147(6):1519-1527. doi: 10.1002/ijc.32899. Epub 2020 Mar 5.
Hepatocellular carcinoma (HCC) is the most common type of primary tumor in the liver and is a leading cause of cancer-related death worldwide. Activated hepatic stellate cells (HSCs) are key components of the HCC microenvironment and play an important role in the onset and progression of HCC through the secretion of growth factors and cytokines. Current treatment modalities that include chemotherapy, radiotherapy and ablation are able to activate HSCs and remodel the tumor microenvironment. Growing evidence has demonstrated that the complex interaction between activated HSCs and tumor cells can facilitate cancer chemoresistance and metastasis. Therefore, therapeutic targeting of activated HSCs has emerged as a promising strategy to improve treatment outcomes for HCC. This review summarizes the molecular mechanisms of HSC activation triggered by treatment modalities, the function of activated HSCs in HCC, as well as the crosstalk between tumor cells and activated HSCs. Pathways of activated HSC reduction are discussed, including inhibition, apoptosis, and reversion to the inactivated state. Finally, we outline the progress and challenges of therapeutic approaches targeting activated HSCs in the development of HCC treatment.
肝细胞癌（HCC）是肝脏中最常见的原发性肿瘤类型，也是全球癌症相关死亡的主要原因。活化的肝星状细胞（HSCs）是 HCC 微环境的关键组成部分，通过分泌生长因子和细胞因子在 HCC 的发生和进展中发挥重要作用。目前的治疗方法包括化疗、放疗和消融，这些方法能够激活 HSCs 并重塑肿瘤微环境。越来越多的证据表明，活化的 HSCs 与肿瘤细胞之间的复杂相互作用可以促进癌症的化疗耐药性和转移。因此，针对活化的 HSCs 的治疗靶向已成为改善 HCC 治疗效果的有前途的策略。本综述总结了治疗方法引发的 HSC 活化的分子机制、活化的 HSCs 在 HCC 中的功能以及肿瘤细胞与活化的 HSCs 之间的串扰。讨论了减少活化的 HSCs 的途径，包括抑制、凋亡和恢复到静止状态。最后，我们概述了针对 HCC 治疗中活化的 HSCs 的治疗方法的进展和挑战。
