Mercury Bioaccumulation in Female Breast Cancer Is Associated to CXCR4 Expression

Int J Mol Sci. 2025 May 7;26(9):4427. doi: 10.3390/ijms26094427.

Abstract

The growing incidence of breast cancer over time suggests that environmental factors might contribute to the underlying causes of the disease. Mercury, a toxic metal classified as a Substance of Very High Concern, accumulates in the body through contaminated food, air, water, and soil, raising concerns about its role in tumor biology. The main aim of this study was to identify the possible associations between in situ mercury bioaccumulation and the molecular features of breast cancer. To achieve this, a total of 26 breast cancer cases were analyzed using an integrated approach that combined DNA and RNA sequencing, histological analysis, and inductively coupled plasma mass spectrometry (ICP-MS) to assess mercury bioaccumulation. Mercury was detected in 72% of the cases. A significant positive correlation was found between mercury bioaccumulation and CXCR4 expression in breast cancer tissues. Bioinformatic analysis further revealed that CXCR4 expression was significantly higher in metastatic tissues compared to primary tumors. These findings suggest that mercury accumulation may influence tumor biology through the CXCR4-CXCL12 signaling pathway, highlighting a potential mechanism by which mercury contributes to breast cancer progression.

Keywords: CXCR4; environmental pollution; heavy metals; mercury.

MeSH terms

  • Adult
  • Aged
  • Breast Neoplasms* / genetics
  • Breast Neoplasms* / metabolism
  • Breast Neoplasms* / pathology
  • Chemokine CXCL12 / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Mercury* / metabolism
  • Mercury* / toxicity
  • Middle Aged
  • Receptors, CXCR4* / genetics
  • Receptors, CXCR4* / metabolism
  • Signal Transduction

Substances

  • Receptors, CXCR4
  • Mercury
  • CXCR4 protein, human
  • Chemokine CXCL12

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