Lactate induced mesenchymal stem cells activation promotes gastric cancer cells migration and proliferation

被引：17

作者：

Tao, Zhixin ^{[1
]}

Huang, Chao ^{[1
]}

Wang, Deqiang ^{[2
]}

Wang, Qianqian ^{[1
]}

Gao, Qiuzhi ^{[1
]}

Zhang, Hao ^{[1
]}

Zhao, Yuanyuan ^{[1
]}

Wang, Mei ^{[1
]}

Xu, Juan ^{[3
]}

Shen, Bo ^{[4
]}

Zhou, Chenglin ^{[3
]}

Zhu, Wei ^{[1
]}

机构：

[1] Jiangsu Univ, Sch Med, Zhenjiang 212000, Jiangsu, Peoples R China

[2] Jiangsu Univ, Jiangsu Univ Inst Digest Dis, Affiliated Hosp, Dept Oncol, Zhenjiang 212001, Jiangsu, Peoples R China

[3] Nanjing Med Univ, Affiliated Taizhou Peoples Hosp, Dept Lab Med, Taizhou 225300, Jiangsu, Peoples R China

[4] Nanjing Med Univ, Jiangsu Canc Hosp, Dept Oncol, Nanjing 210009, Jiangsu, Peoples R China

来源：

EXPERIMENTAL CELL RESEARCH | 2023年 / 424卷 / 01期

基金：

中国国家自然科学基金;

关键词：

Lactate; Mesenchymal stem cells; Monocarboxylate transporter 1; Gastric cancer; Fibroblast activation protein; PD-L1; TUMOR MICROENVIRONMENT; FIBROBLASTS; EXPRESSION;

D O I：

10.1016/j.yexcr.2023.113492

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Lactate extensively involves in gastric cancer (GC) progression, such as suppressing immune cells function and facilitating tumor angiogenesis. However, it remains unclear whether lactate promotes tumor progression by interacting with mesenchymal stem cells (MSCs), one of the major stroma components in GC. Here, we investigated the influence of lactate on the phenotype and function of MSCs. The migration of MSCs and the expression of several CAF markers in MSCs after lactate treatment were detected. We also evaluated the effect of lactate-primed MSCs on GC cells migration, proliferation, and programmed death ligand 1 (PD-L1) expression. It was found that lactate significantly activated MSCs, and increased fibroblast activation protein (FAP) expression via monocarboxylate transporter 1 (MCT1)/transforming growth factor-beta 1 (TGF-81) signaling. In addition, lactate-primed MSCs promoted GC cells migration and proliferation via PD-L1. Inhibiting MCT1 by AZD3965 abrogated lactate induced FAP expression and tumor-promoting potential of MSCs. Therefore, targeting MCT1/ TGF-81/FAP axis in MSCs may serve as a potential strategy to restrain GC development.

引用

页数：9

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