Polyethylene terephthalate microplastics induce immune evasion and malignant remodeling in breast cancer through
Ying-Chuan Yin1, Wang Zhang2, Jing He1
1Department of Endocrinology, The Third People's Hospital of Hefei, Hefei Third Clinical College of Anhui Medical University, Hefei, 230022, China.
Abstract:
Polyethylene terephthalate (PET) microplastics (MPs) have emerged as a significant environmental contaminant with potential adverse effects on human health, particularly in cancer biology. This study investigates the molecular and immunological mechanisms underlying the influence of PET-MPs on breast cancer (BC) progression. Employing an integrative approach that combines bioinformatics analysis of public cancer databases (TCGA), molecular docking simulations, and in vitro experiments, we identified four immune-related genes-CCL19, KLRB1, CD40LG, and IGLL5-that are potentially modulated by PET-MPs. Molecular docking indicated that bis(2-hydroxyethyl) terephthalate (BHET), a key PET oligomer, binds with high affinity to these proteins, suggesting that PET-MPs may alter immune homeostasis within the tumor microenvironment (TME). Additionally, PET-MPs induced a pro-inflammatory cytokine response, including elevated IL-6 and TNF-α secretion, which could promote tumor progression. Our findings further suggest that PET-MPs may enhance BC cell proliferation and survival through immune modulation. However, limitations include the lack of immune cell co-culture models and in vivo validation. This study provides essential insights into the immunotoxicity of PET-MPs and highlights the need for further research to explore their direct and indirect effects on cancer development.
Insights
Polyethylene terephthalate (PET) microplastics (MPs) may impact breast cancer by altering immune responses and promoting tumor growth. Further research is needed to understand these immunotoxic effects on cancer development.
Area of Science:
- Environmental Health
- Cancer Biology
- Immunology
Background:
- Microplastics (MPs), particularly from polyethylene terephthalate (PET), are emerging environmental contaminants.
- Growing concerns exist regarding their potential adverse effects on human health, especially in cancer biology.
Purpose of the Study:
- To investigate the molecular and immunological mechanisms by which PET MPs influence breast cancer (BC) progression.
- To identify specific immune-related genes and pathways affected by PET MPs.
Main Methods:
- Integrative approach combining bioinformatics analysis of The Cancer Genome Atlas (TCGA) database.
- Molecular docking simulations to assess interactions between PET oligomers and immune proteins.
- In vitro experiments to evaluate the effects of PET MPs on cytokine secretion and cancer cell behavior.
Main Results:
- Identified four immune-related genes (CCL19, KLRB1, CD40LG, IGLL5) potentially modulated by PET MPs.
- Bis(2-hydroxyethyl) terephthalate (BHET), a PET oligomer, showed high-affinity binding to these immune proteins.
- PET MPs induced pro-inflammatory cytokines (IL-6, TNF-α) and enhanced BC cell proliferation and survival.
Conclusions:
- PET MPs may promote breast cancer progression through immune modulation and altering the tumor microenvironment (TME).
- Findings highlight the immunotoxicity of PET MPs, necessitating further investigation into their role in cancer development.
- Limitations include the absence of in vivo validation and immune cell co-culture models.
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