Jayachandran Jayenth, Rithi A T, Mitra Abhijit, Radhakrishnan Arunkumar, Banerjee Antara, Duttaroy Asim K
Department of Pharmacology, Chettinad Hospital and Research Institute (CHRI), Chettinad Academy of Research and Education (CARE), Chennai, India.
Medical Biotechnology Lab, Faculty of Allied Health Sciences, Chettinad Hospital and Research Institute (CHRI), Chettinad Academy of Research and Education (CARE), Chennai, 603103, India.
Discov Oncol. 2025 Jul 7;16(1):1276. doi: 10.1007/s12672-025-03088-9.
Hepatocellular carcinoma (HCC) is a significant global health challenge, being one of the leading causes of cancer-related mortality. This review focuses on the intricate interactions within the tumor microenvironment and mesenchymal stem cells (MSCs) and it's secretome in HCC and possible therapeutic responses. MSCs, characterized by their multipotent differentiation and self-renewal capabilities, can influence tumor behavior maybe through its secreted factors, including cytokines, growth factors and extracellular vesicles. This review summarizes the recent findings on role of MSCs in HCC, highlighting its involvement in different cell signaling pathways, including NF-κB, Wnt/β-catenin, Notch1, Stat3, and TGF-β, which play a significant role in HCC and possibly exhibit both tumor-suppressive and/or tumor-promoting effects depending on the activation or deactivation of signaling pathways. Publications related to the topic between 2016 to 2025 were searched using databases like PubMed, Scopus, Google Scholar with keywords viz. HCC, mesenchymal stem cells, secretome, tumor microenvironment, and signaling pathways. Findings from different research studies depict that MSCs and their secretome can exert anti-tumor effects by inducing apoptosis and enhancing immune responses, they may also promote alternate effects like tumor proliferation and metastasis under certain conditions, related to the activation or deactivation of different signalling pathways. This review aims to provide a comprehensive understanding of the multifaceted roles of MSCs in HCC. The dual role and the complexities of MSCs is context dependent. However, advancements in MSC research showed that the modifications of MSCs and secretome-based therapies and targeting the signaling pathways may have the potential to overcome challenges like drug resistance in HCC treatment.
肝细胞癌（HCC）是一项重大的全球健康挑战，是癌症相关死亡的主要原因之一。本综述聚焦于肝癌肿瘤微环境与间充质干细胞（MSCs）及其分泌组之间的复杂相互作用以及可能的治疗反应。MSCs具有多能分化和自我更新能力，可能通过其分泌因子（包括细胞因子、生长因子和细胞外囊泡）影响肿瘤行为。本综述总结了MSCs在肝癌中作用的最新研究结果，强调其参与不同的细胞信号通路，包括NF-κB、Wnt/β-连环蛋白、Notch1、Stat3和TGF-β，这些通路在肝癌中起重要作用，并且根据信号通路的激活或失活可能表现出肿瘤抑制和/或肿瘤促进作用。使用PubMed、Scopus、谷歌学术等数据库，以肝癌、间充质干细胞、分泌组、肿瘤微环境和信号通路等关键词搜索了2016年至2025年期间与该主题相关的出版物。不同研究的结果表明，MSCs及其分泌组可通过诱导凋亡和增强免疫反应发挥抗肿瘤作用，但在某些条件下，与不同信号通路的激活或失活相关，它们也可能促进肿瘤增殖和转移等其他效应。本综述旨在全面了解MSCs在肝癌中的多方面作用。MSCs的双重作用和复杂性取决于具体情况。然而，MSCs研究的进展表明，对MSCs和基于分泌组的疗法进行修饰以及靶向信号通路可能有潜力克服肝癌治疗中的耐药性等挑战。
