The Therapeutic Potential of Adipose Tissue-Derived Mesenchymal Stem Cells to Enhance Radiotherapy Effects on Hepatocellular Carcinoma

• Main Authors: Lingyun Wu, Qiuying Tang, Xin Yin, DanFang Yan, Mengmeng Tang, Jiaojiao Xin, Qiaoling Pan, Chiyuan Ma, Senxiang Yan
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2019-11-01
• Series: Frontiers in Cell and Developmental Biology
• Subjects: adipose tissue-derived mesenchymal stem cells; radiotherapy; hepatocellular carcinoma; interferon-induced transmembrane 1; combination therapy
• Online Access: https://www.frontiersin.org/article/10.3389/fcell.2019.00267/full

Several studies have investigated strategies to improve the clinical efficacy of radiotherapy (RT) against hepatocellular carcinoma (HCC), yet the prognosis remains poor. Human adipose tissue-derived mesenchymal stem cells (AT-MSCs), easily accessible and abundant in quantity, have represented as an attractive therapeutic tool for the stem cell-based treatment for cancer diseases. Through direct co-culture and indirect separate culture experiments, we showed that AT-MSCs could enhance inhibitory effect of RT on reducing HCC cell growth, migration and invasion in both in vitro and in vivo experiments. RNA-sequencing analysis revealed a noticeable interferon-induced transmembrane 1 (IFITM1)-induced tumor gene signature. Gain and loss of mechanistic studies indicated that mechanism was attributed to downregulated expression of signal transducer and activator of transcription 3 (STAT3) and matrix metallopeptidases (MMPs) and upregulated expression of P53 and caspases. Collectively, our findings suggest that AT-MSCs might enhance the therapeutic effects of RT on HCC, providing a rationale for AT-MSCs and RT combination therapy as a new remedy for HCC.