Polyethylene microplastics trigger osteosarcoma progression via ITGA5/FAPα/LGMN cancer promoting complex: A novel environmental cancer promoting mechanism

This study seeks to elucidate the molecular mechanisms by which polyethylene microplastics (PE-MPs) facilitate the progression of osteosarcoma through the modulation of the ITGA5/FAPα/LGMN protein complex. Initially, tumor tissues were obtained from patients diagnosed with osteosarcoma, and Raman spectroscopy was employed to identify and characterize the presence of microplastics. Subsequent observations revealed that PE-MPs were internalized by osteosarcoma cells, exhibiting a pronounced promotive effect on cancer progression at a concentration of 10 mg/L. High-throughput sequencing analysis revealed that PE-MPs specifically upregulated the expression level of the ITGA5 gene. Immunofluorescence staining and co-immunoprecipitation (Co-IP) experiments further confirmed that ITGA5, FAPα, and LGMN interact to form a complex within osteosarcoma cells, and their protein expression levels increased in a dose-dependent manner with increasing polyethylene particle concentration. Furthermore, in vivo animal experiments demonstrated that polyethylene particle treatment significantly enhanced tumor growth, while administration of inhibitors targeting ITGA5, FAPα, or LGMN partially alleviated this pro-carcinogenic effect. This study first discovered the presence of microplastic particles in human osteosarcoma and elucidated the molecular mechanism by which PE-MPs promote osteosarcoma progression through interaction with ITGA5/FAPα/LGMN complex. This discovery provides new insights into the mechanism of action of environmental carcinogens and important theoretical support for the development of precise treatment strategies and prognostic biomarkers in the microenvironment of osteosarcoma.