转移
淋巴管新生
愤怒(情绪)
癌症研究
医学
癌症
肝细胞癌
淋巴系统
血管内皮生长因子C
病理
生存素
癌细胞
血管内皮生长因子
血管内皮生长因子A
生物
血管内皮生长因子受体
内科学
神经科学
作者
TianYi Chen,Yeling Ruan,Lin Ji,Jingwei Cai,Meng Tong,YangTao Xue,Hu Zhao,Xiujun Cai,Junjie Xu
出处
期刊:Cancer Letters
[Elsevier]
日期:2024-02-01
卷期号:: 216709-216709
被引量:1
标识
DOI:10.1016/j.canlet.2024.216709
摘要
Patients diagnosed with lymph node (LN) metastatic liver cancer face an exceedingly grim prognosis. In-depth analysis of LN metastatic patients' characteristics and tumor cells’ interactions with human lymphatic endothelial cells (HLECs), can provide important biological and therapeutic insights. Here we identify at the single-cell level that S100A6 expression differs between primary tumor and their LN metastasis. Of particular significance, we uncovered the disparity in S100A6 expression between tumors and normal tissues is greater in intrahepatic cholangiocarcinoma (ICC) patients, frequently accompanied by LN metastases, than that in hepatocellular carcinoma (HCC), with rare occurrence of LN metastasis. Furthermore, in the infrequent instances of LN metastasis in HCC, heightened S100A6 expression was observed, suggesting a critical role of S100A6 in the process of LN metastasis. Subsequent experiments further uncovered that S100A6 secreted from tumor cells promotes lymphangiogenesis by upregulating the expression and secretion of vascular endothelial growth factor-D (VEGF-D) in HLECs through the RAGE/NF-kB/VEGF-D pathway while overexpression of S100A6 in tumor cells also augmented their migration and invasion. Taken together, these data reveal the dual effects of S100A6 in promoting LN metastasis in liver cancer, thus highlighting its potential as a promising therapeutic target.
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