基质
间质细胞
神经内分泌肿瘤
转移
表型
肿瘤微环境
癌症研究
肿瘤进展
病理
生物
胰腺癌
医学
癌症
免疫组织化学
肿瘤细胞
遗传学
基因
生物化学
作者
Ye Zeng,Qiang Li,Yuheng Hu,Haifeng Hu,Junfeng Xu,Mingzhou Guo,Wuhu Zhang,Xin Lou,Yan Wang,Heli Gao,Desheng Jing,Guixiong Fan,Yi Qin,Yue Zhang,Xuemin Chen,Jie Chen,Xiaowu Xu,Lei Yu,Mingyang Liu,Shunrong Ji
标识
DOI:10.1016/j.canlet.2024.216769
摘要
Cancer-associated fibroblasts (CAFs) play an important role in a variety of cancers. However, the role of tumor stroma in nonfunctional pancreatic neuroendocrine tumors (NF-PanNETs) is often neglected. Profiling the heterogeneity of CAFs can reveal the causes of malignant phenotypes in NF-PanNETs. Here, we found that patients with high stromal proportion had poor prognosis, especially for that with infiltrating stroma (stroma and tumor cells that presented an infiltrative growth pattern and no regular boundary). In addition, myofibroblastic CAFs (myCAFs), characterized by FAP+ and α-SMAhigh, were spatially closer to tumor cells and promoted the EMT and tumor growth. Intriguingly, only tumor cells which were spatially closer to myCAFs underwent EMT. We further elucidated that myCAFs stimulate TGF-β expression in nearby tumor cells. Then, TGF-β promoted the EMT in adjacent tumor cells and promoted the expression of myCAFs marker genes in tumor cells, resulting in distant metastasis. Our results indicate that myCAFs cause spatial heterogeneity of EMT, which accounts for liver metastasis of NF-PanNETs. The findings of this study might provide possible targets for the prevention of liver metastasis.
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