CD34+CLDN5+ tumor associated senescent endothelial cells through IGF2-IGF2R signaling increased cholangiocellular phenotype in hepatocellular carcinoma

作者：Xin-yu Zhu, Wenting Liu, Xiaojuan Hou, Chen Zong, Wei Yu, Zhemin Shen, Shuping Qu, Min Hui Tao, Meiling Xue, Dao-yu Zhou, Hao-ran Bai, Lu Gao, Jinghua Jiang, Qiudong Zhao, Lixin Wei, Xue Yang, Zhipeng Han, Li Zhang · 发表于：Journal of Advanced Research · 年份：2024 · DOI：10.1016/j.jare.2024.12.008 · 被引用次数：13 · 研究领域：Cholangiocarcinoma and Gallbladder Cancer Studies、Cancer Cells and Metastasis、Telomeres, Telomerase, and Senescence

• Utilizing single-cell RNA sequencing technology, we have identified a distinct subset of tumor-associated senescent endothelial cells. • This study demonstrated that senescent endothelial cells increased the cholangiocellular phenotype within hepatocellular carcinoma. • This study reveals that the cross-talk between the senescent endothelial cells and mesenchymal stem cells fostered the tumor progression. • Senescent endothelial cells recruited mesenchymal stem cells into the tumor microenvironment via IGF2-IGF2R signaling. The heterogeneity of hepatocellular carcinoma (HCC) is linked to tumor malignancy and poor prognosis. Nevertheless, the precise mechanisms underlying the development of the cholangiocellular phenotype (CCA) within HCC remain unclear. Emerging studies support that the cross-talk among the host cells within tumor microenvironment (TME) sustains the cancer cell plasticity. This study sought to identify the specific cell types involved in the formation of CCA and to elucidate their functional roles in the progression of HCC. S ingle-cell RNA sequencing was employed to identify the specific cell types involved in the formation of CCA. Both in vitro and vivo analyses were used to identify the tumor-associated senescent ECs and investigate the function in TME. The diethylnitrosamine-induced model was utilized to investigate the interaction between senescent ECs and MSCs, aiming to elucidate their synergistic contributions to the progression of CCA. Using single...