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Research Paper|Volume 15, Issue 24|pp 15525—15534

M-CSF secreted by gastric cancer cells exacerbates the progression of gastric cancer by increasing the expression of SHP2 in tumor-associated macrophages

Shaohua Zhang1, Dongfei Ren1, Huiyu Hou2, Li Yao3, Hufang Yuan4
  • 1Eighth People’s Hospital of Hebei Province, Shijiazhuang 050000, China
  • 2HeBei General Hospital, Shijiazhuang 050000, China
  • 3Handan Central Hospital, Handan 056000, China
  • 4The Fourth Hospital of Hebei Medical University, Shijiazhuang 050000, China
* Equal contribution
Received: June 26, 2023Accepted: October 23, 2023Published: December 29, 2023
https://doi.org/10.18632/aging.205390

Copyright: © 2023 Zhang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Objective: To investigate the effect of Src homology 2 domain-containing tyrosine phosphatase-2 (SHP2) in tumor-associated macrophages (TAMs), which is mediated by macrophage colony-stimulating factor (M-CSF) secreted by gastric cancer cells, on the development of gastric cancer and its molecular mechanism.

Methods: The progression of gastric cancer was detected by nude mouse tumor-bearing experiments. Colony formation assay and cell counting kit-8 (CCK8) assay were used to detect the proliferation capacity of gastric cancer cells. The migration capacity of gastric cancer cells was examined by wound healing assay. Transwell migration and invasion assays were performed on gastric cancer cells. Detection of relevant protein expression using western blotting.

Results: Overexpression of SHP2 could promote the progression of gastric cancer in nude mice. The results of colony formation assay and CCK8 assay showed that overexpression of SHP2 could enhance the proliferation of gastric cancer cells. It was found by wound healing assay and Transwell assay that overexpression of SHP2 could facilitate the migration and invasion of gastric cancer cells. The results of Western blotting revealed that overexpression of SHP2 could increase the expressions of p-STAT3, s-PD-1, p-Src, p-Lyn, p-PI3K, p-AKT, Arginase-1, MMP1 and MMP3 but decrease the expressions of TBK1 and SOCS1 in TAMs, and also increase the expressions of CD9, TSG101 and s-PD-1 in exosomes.

Conclusion: M-CSF secreted by gastric cancer cells can promote the proliferation, invasion and migration of gastric cancer cells by increasing the expression of SHP2 in TAMs.