2. Academic Validation
  3. CALB2 facilitates macrophage M2 polarization to promote the growth and metastasis of pancreatic adenocarcinoma

CALB2 facilitates macrophage M2 polarization to promote the growth and metastasis of pancreatic adenocarcinoma

  • Cell Signal. 2025 Oct:134:111887. doi: 10.1016/j.cellsig.2025.111887.
Dongwei Hu 1,  Bo Xu 2,  Guoyu Huang 3,  Xiaowei Hu 1,  Jinjie Li 2,  Zongjing Chen 2,  Wei Liu 4,  Zhengde Wen 5
Affiliations

Affiliations

  • 1 Department of Clinical Laboratory, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, PR China; Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province, Wenzhou, Zhejiang 325000, PR China.
  • 2 Department of Hepato-pancreato-biliary Surgery, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, PR China.
  • 3 Division of Vascular and Interventional Radiology, Laboratory for Patient Inspired Engineering, Mayo Clinic, 13400 East Shea Blvd., Scottsdale, AZ 85259, USA.
  • 4 Institute of Digestive Disease, China Three Gorges University, Yichang, PR China. Electronic address: liuwei@ctgu.edu.cn.
  • 5 Department of Hepato-pancreato-biliary Surgery, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, PR China; Wenzhou Key Laboratory of Perioperative Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, PR China. Electronic address: wenzhengde58@163.com.
PMID: 40409389 DOI: 10.1016/j.cellsig.2025.111887
Abstract

Tumor-associated macrophages mainly differentiate into M2 phenotypes, which secrete cytokines that reshape the tumor microenvironment and promote tumor progression. This study was to explore the mechanism of CALB2 in M2 polarization and pancreatic adenocarcinoma (PAAD). Clinical tissue samples of PAAD were collected, followed by detection of WTAP, FOSL1, and CALB2 expression. The correlation between WTAP and FOSL1 or between FOSL1 and CALB2 was analyzed. THP1 cells were induced into M0 macrophages, followed by plasmid transfection and induction of M2-type macrophages. After macrophages were co-cultured with PAAD cells, functional experiments were designed to evaluate PAAD cell malignant behaviors. A transplantation tumor model and a liver metastasis model were established to assess tumor growth and metastasis. High expression of WTAP, FOSL1, and CALB2 was found in PAAD tissues and M2-type macrophages. WTAP positively linked with FOSL1, so as FOSL1 and CALB2. Mechanistically, WTAP enhanced m6A modification of FOSL1 to promote its expression, and FOSL1 promoted CALB2 transcription. Knockdown of WTAP, FOSL1, or CALB2 in macrophages inhibited PAAD cell malignant behaviors, which could be reversed by CALB2 upregulation. WTAP knockdown restrained the growth and metastasis of PAAD in nude mice via the FOSL1/CALB2 axis. In conclusion, WTAP increased the m6A level of FOSL1, activated CALB2 transcription, and promoted M2 polarization of macrophages, thereby promoting the growth and metastasis of PAAD.

Keywords

CALB2; FOSL1; Pancreatic adenocarcinoma; WTAP; m(6)A modification.

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