Polystyrene Microplastics Exposure Aggravates Clear Cell Renal Cell Carcinoma Progression via the NF-κB and TGF-β...

Area of Science:

• Environmental Science
• Oncology
• Toxicology

Background:

• Polystyrene microplastics (PS-MPs) are emerging environmental contaminants.
• Their specific role in clear cell renal cell carcinoma (ccRCC) pathogenesis is largely unknown.
• Understanding PS-MPs' impact on ccRCC is crucial for public health.

Purpose of the Study:

• To investigate the presence and impact of PS-MPs in ccRCC tissues.
• To elucidate the molecular mechanisms by which PS-MPs influence ccRCC progression.
• To evaluate potential therapeutic strategies against PS-MPs-induced ccRCC.

Main Methods:

• Detection of PS-MPs in ccRCC tissues and normal adjacent tissues (NAT) using Py-GC/MS, LDIR, and SEM.
• Assessment of PS-MPs' effects on ccRCC cellular behaviors via functional assays.
• Transcriptomic analysis (RNA-seq) to identify molecular alterations.
• Investigation of signaling pathways (NF-κB, TGF-β) using immunoblotting, immunocytochemistry, and ELISA.
• Evaluation in preclinical PDO and CDX models.

Main Results:

• PS-MPs were significantly more abundant in ccRCC tissues than in NAT.
• Cytoplasmic accumulation of PS-MPs promoted malignant phenotypes in ccRCC cells.
• PS-MPs exposure activated oncogenic pathways, specifically NF-κB and TGF-β.
• Preclinical models showed PS-MPs accelerated ccRCC growth, which was mitigated by pathway inhibitors.

Conclusions:

• This study provides the first comprehensive evidence linking PS-MPs to ccRCC progression.
• PS-MPs exacerbate ccRCC by activating the NF-κB and TGF-β signaling pathways.
• PS-MPs are identified as an environmental risk factor for ccRCC, with potential therapeutic targets.