2. Academic Validation
  3. Lactate induced mesenchymal stem cells activation promotes gastric cancer cells migration and proliferation

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

  • Exp Cell Res. 2023 Jan 24;424(1):113492. doi: 10.1016/j.yexcr.2023.113492.
Zhixin Tao 1,  Chao Huang 1,  Deqiang Wang 2,  Qianqian Wang 1,  Qiuzhi Gao 1,  Hao Zhang 1,  Yuanyuan Zhao 1,  Mei Wang 1,  Juan Xu 3,  Bo Shen 4,  Chenglin Zhou 5,  Wei Zhu 6
Affiliations

Affiliations

  • 1 School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, 212000, China.
  • 2 Department of Oncology, Affiliated Hospital of Jiangsu University; Institute of Digestive Diseases, Jiangsu University, Zhenjiang, Jiangsu, 212001, China.
  • 3 Department of Laboratory Medicine, Affiliated Taizhou People's Hospital of Nanjing Medical University, Taizhou, Jiangsu, 225300, China.
  • 4 Department of Oncology, Jiangsu Cancer Hospital Affiliated to Nanjing Medical University, Nanjing, Jiangsu, 210009, China.
  • 5 Department of Laboratory Medicine, Affiliated Taizhou People's Hospital of Nanjing Medical University, Taizhou, Jiangsu, 225300, China. Electronic address: [email protected].
  • 6 School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, 212000, China. Electronic address: [email protected].
PMID: 36702194 DOI: 10.1016/j.yexcr.2023.113492
Abstract

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-β1) 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-β1/FAP axis in MSCs may serve as a potential strategy to restrain GC development.

Keywords

Fibroblast activation protein; Gastric cancer; Lactate; Mesenchymal stem cells; Monocarboxylate transporter 1; PD-L1.

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