Polyethylene terephthalate nanoplastics promote colorectal tumor progression and are associated with a CEMIP high cancer-associated fibroblast population

The effects of polyethylene terephthalate nanoplastics (PET-NPs) on colorectal cancer (CRC) progression remain poorly understood. This study investigated the effects of chronic PET-NP exposure using an azoxymethane/dextran sodium sulfate (AOM/DSS)-induced mouse model of CRC and complementary in vitro experiments. PET-NP exposure increased tumor burden, aggravated histopathological alterations, and elevated malignancy-associated marker expression in mice. Single-cell RNA sequencing revealed PET-NP-associated differences in inferred copy number variation signals and tumor cell composition. Fibroblasts showed the highest number of inferred outgoing cell–cell interactions in the PET-NP-exposed group. Fibroblast subclustering identified a CEMIP-high cancer-associated fibroblast (CAF) population with a higher pooled proportion in PET-NP-exposed tumors. In vitro, PET-NP exposure enhanced malignant phenotypes in DLD-1 cells and increased CEMIP, MMP-2, and MMP-9 protein expression in primary human CAFs. A reduced fluorescence signal from Cy5-labeled hyaluronic acid was also observed in CAF culture supernatants following PET-NP exposure. Under simultaneous PET-NP exposure, DLD-1 cells co-cultured with primary human CAFs exhibited greater migration, invasion, and epithelial–mesenchymal transition-associated changes than DLD-1 cells cultured without CAFs. Together, these findings support a tumor-promoting effect of PET-NPs in an established mouse CRC model and identify accompanying changes in CAF populations and CRC cell behavior. Further functional studies are needed to establish the contribution of CEMIP to these effects. Clinical trial number: Not applicable.