成纤维细胞
细胞
基因沉默
癌症研究
细胞生物学
癌相关成纤维细胞
肿瘤微环境
生物
细胞迁移
细胞生长
细胞培养
化学
基因
肿瘤细胞
遗传学
作者
Qiqi Cao,Jinxian Yang,Lixuan Jiang,Zhao Yang,Zhecai Fan,Shuzhen Chen,Sibo Zhu,Lei Yin,Hongyang Wang,Wen Wen
摘要
The incidence rate of intrahepatic cholangiocarcinoma (ICC), which has a poor prognosis, is rapidly increasing. To investigate the intratumor heterogeneity of ICC, we analyzed single-cell RNA sequencing data from the primary tumor and adjacent normal tissues of 14 treatment-naïve patients. We identified ten major cell types, along with 45 subclusters of cells. Notably, we identified a fibroblast cluster, Fibroblast_LUM+, which was preferably enriched in tumor tissues and actively interacted with cholangiocytes. LGALS1 was verified as a marker gene of Fibroblast_LUM+, contributing to the malignant phenotype of ICC. The higher amount of LGALS1 + fibroblasts were associated with poorer overall survival in ICC patients. LGALS1 + fibroblasts activated the proliferation and migration of tumor cells by upregulating the expression levels of CCR2, ADAM15, and β-integrin. Silencing LGALS1 in cancer-associated fibroblasts (CAFs) suppressed CAF-augmented tumor cell migration and invasion in vitro as well as tumor formation in vivo, suggesting that blockade of LGALS1 serves as a potential therapeutic approach for ICC. Taken together, our single-cell analysis provides insight into the interaction between malignant cells and specific subtypes of fibroblasts. Our work will further the understanding of the intratumor heterogeneity of ICC and provide novel strategies for the treatment of ICC by targeting fibroblasts in the tumor microenvironment.
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