2. Academic Validation
  3. PFDA promotes cancer metastasis through macrophage M2 polarization mediated by Wnt/β-catenin signaling

PFDA promotes cancer metastasis through macrophage M2 polarization mediated by Wnt/β-catenin signaling

  • Chemosphere. 2024 Jul 3:362:142758. doi: 10.1016/j.chemosphere.2024.142758.
Zhenyan Cui 1,  Zekun Liu 1,  Xiaoyu Yuan 1,  Kean Lu 1,  Mengyao Li 1,  Sinan Xu 1,  Kelie Chen 2,  Fang Zheng 2,  Ying Li 3,  Paul Héroux 3,  Yihua Wu 4,  Dajing Xia 5
Affiliations

Affiliations

  • 1 Department of Toxicology of School of Public Health, Department of Gynecologic Oncology of Women's Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  • 2 Department of Gynecology and Obstetrics, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  • 3 Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Canada.
  • 4 Department of Toxicology of School of Public Health, Department of Gynecologic Oncology of Women's Hospital, Zhejiang University School of Medicine, Hangzhou, China; Research Unit of Intelligence Classification of Tumor Pathology and Precision Therapy, Chinese Academy of Medical Sciences, Hangzhou, China. Electronic address: georgewu@zju.edu.cn.
  • 5 Department of Toxicology of School of Public Health, Department of Gynecologic Oncology of Women's Hospital, Zhejiang University School of Medicine, Hangzhou, China; Cancer Center, Zhejiang University, Hangzhou, China. Electronic address: dxia@zju.edu.cn.
PMID: 38969224 DOI: 10.1016/j.chemosphere.2024.142758
Abstract

Perfluoroundecanoic acid (PFDA) is extensively utilized in the textile and food processing industries and may have a tumor-promoting effect by modulating the tumor microenvironment. Macrophages play crucial roles in tumor microenvironment as key regulators of tumor immunity. However, further investigation is needed to elucidate how PFDA interacts with macrophages and contributes to tumor progression. In this study, we treated the macrophage cell line RAW264.7 with various concentrations of PFDA and found that RAW264.7 transitioned into an M2 tumor-promoting phenotype. Through bioinformatic analysis and subsequent verification of molecular assays, we uncovered that PFDA could activate β-catenin and enhance its nuclear translocation. Additionally, it was also observed that inhibiting β-catenin nuclear translocation partly attenuated RAW264.7 M2 polarization induced by PFDA. The conditioned medium derived from PFDA-pretreated RAW264.7 cells significantly promoted the migration and invasion abilities of human ovarian Cancer cells. Furthermore, in vivo studies corroborated that PFDA-pretreated RAW264.7 could promote tumor metastasis, which could be mitigated by pretreatment with the β-catenin Inhibitor ICG001. In conclusion, our study demonstrated that PFDA could promote Cancer metastasis through regulating macrophage M2 polarization in a Wnt/β-catenin-dependent manner.

Keywords

M2 macrophage; Ovarian cancer; PFDA.

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