ORIGINAL RESEARCH article

Front. Oncol.

Sec. Molecular and Cellular Oncology

Volume 15 - 2025 | doi: 10.3389/fonc.2025.1585935

SerpinE2 promotes M2 polarization in macrophage to accelerate colorectal cancer progression

Provisionally accepted
Hui-Long  LiuHui-Long Liu1XiaoSheng  GaoXiaoSheng Gao1WeiFeng  YangWeiFeng Yang1Wang-Lin  LiWang-Lin Li2*
  • 1Department of Colorectal Surgery, the Second Affiliated Hospital of South China University of Technology, Guangzhou, Guangdong, China., Guangzhou, China
  • 2School of Medicine, South China University of Technology, Guangzhou, China

The final, formatted version of the article will be published soon.

Cell-cell crosstalk in the tumor microenvironment (TME) is crucial for cancer development and strongly correlates with clinical outcomes. Interpatient variability in tumor microenvironment composition and function poses ongoing challenges for personalized therapy selection, remaining a significant clinical problem.Serpin family E member 2 (SERPINE2) released from the tumor microenvironment exhibits significant regulatory functions in cancer progression but the role of SERPINE2 in the tumor microenvironment remains unclear. In this study, we want to investigate the potential mechanism of SERPINE2 in tumor microenvironment of colon cancer.Bioinformatics analysis was used for exploring the mRNA expression level of SERPINE family in Pan-cancer, the prognostic significance of SERPINE family overexpression in four cancer types, the clinical relevance of SERPINE2 and the potential function of SERPINE2 in colorectal cancer. We conducted qRT-PCR, Western blot and ELISA to investigate the expression of SERPINE2.Additionally, Tissue chips, Transwell assays, Cell counting kit-8 assay, and co-culture system were used to evaluate the relationship between SERPINE2 and polarization of tumor-associated macrophages .Based on public database screening, the SERPINE family genes were significantly upregulated in various cancers, and high expression of SERPINE family genes in colorectal cancer was closely associated with poor prognosis. Compared to other family members, SERPINE2 showed a high expression level and was closely related to clinical malignant progression of colon cancer patients. co-expression network analysis, KEGG and GO analysis revealed that SERPINE2 expression correlates with tumor immunoregulation, division and proliferation. Immune infiltration analysis indicated a significant positive correlation between SERPINE2 and M2 macrophage infiltration, and tissue chip confirmed the correlation between SERPINE2 expression in colon cancer tissues and macrophage infiltration. Cell co-culture experiments further demonstrated that SERPINE2 secreted by colon cancer cells can induce polarization of M2 macrophages. Next, the recombinant protein SERPINE2 was observed to stimulate macrophage polarization. We found macrophages induced by SERPINE2 in co-culture with cancer cells accelerated cancer cell proliferation and migration.Our study demonstrates that tumor-secreted SERPINE2 mediates a positive feedback loop between tumor cells and M2 macrophages to accelerate cancer progression, suggesting SERPINE2 may be as a promising therapeutic target for colon cancer treatment.

Keywords: Keyword:Colon cancer, SerpinE2, Tumor-associated macrophages, Immune infiltration, M2 polarization

Received: 01 Mar 2025; Accepted: 28 Apr 2025.

Copyright: © 2025 Liu, Gao, Yang and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Wang-Lin Li, School of Medicine, South China University of Technology, Guangzhou, China

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