2. Academic Validation
  3. Galectin-9 promotes colon cancer development by polarizing macrophages toward the M2 phenotype

Galectin-9 promotes colon cancer development by polarizing macrophages toward the M2 phenotype

  • Cancer Genet. 2025 Sep 10:298-299:141-150. doi: 10.1016/j.cancergen.2025.09.006.
Jun Zhang 1,  Yang Xu 2,  Xiao Han 3,  Yan Gao 4,  Zhanbo Wei 5,  Xu Sun 6
Affiliations

Affiliations

  • 1 The Second Department of Surgery, the People's Hospital of Huaiyin Jinan, Jinan, China.
  • 2 Department of General Surgery, The 960th Hospital of Joint Logistics Support Force of PLA, Jinan, China.
  • 3 Department of Radiation Oncology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China.
  • 4 Department of Pathology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China.
  • 5 Yinfeng Gene Technology Co Ltd, Jinan, China.
  • 6 Department of Gastric Surgery, Shandong Cancer Hospital and Institute, Jinan, China; Shandong Frist Medical University and Shandong Academy of Medical Sciences, Jinan, China. Electronic address: sunxuzmz@163.com.
PMID: 41005040 DOI: 10.1016/j.cancergen.2025.09.006
Abstract

Galectin-9 plays multiple roles in various tumors and exerts immune regulation within the tumor microenvironment. It is closely associated with tumor prognosis. This study aimed to analyze the expression of Galectin-9 in the colon tumor microenvironment. The results indicated that Galectin-9 expression is higher in the colon tumor microenvironment compared to adjacent normal tissues. Furthermore, high expression of Galectin-9 was related to M2-type macrophages, which promote tumor development by increasing tumor cell viability, migration, and invasion. Notably, high expression of Galectin-9 in colon tumor microenvironment contributed to the polarization of M2 cells, marked by high expression of arginase-1, CD163, and IL-10 and low expression of iNOS. When M0 macrophages were treated with Galectin-9 and co-cultured with colon Cancer cell lines, it resulted in increased Cancer cell growth, migration, and invasion by promoting the differentiation of THP-1 monocytes into the M2 macrophages. The specific mechanism by which Galectin-9 promotes M2 polarization involves its binding to TIM-3, recruiting PI3K-p85 to the cytoplasmic domain of TIM-3. This interaction further affects the PI3K/Akt signal pathway, leading to M2 polarization.

Keywords

Colon cancer; Galectin-9; Macrophage; PI3K/AKT pathway; Tim-3.

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