TGF-β Induced by Allergic Lung Inflammation Enhances Os-Teosarcoma Lung Metastasis in a Mouse Comorbidity Model.

TGF-β is a central mediator of pulmonary allergic inflammation recently associated with lung metastasis of osteosarcoma. Given the controversial links between cancer and allergic diseases, this study aimed to evaluate the effects of allergic airway inflammation-particularly TGF-β-on osteosarcoma lung metastasis using a comorbidity mouse model. Osteosarcoma cells were implanted in BALB/c mice with induced allergic airway inflammation. Lung metastasis was quantified, while PCNA/TGF-β expression was assessed by immunohistochemistry and digital pathology. Bioinformatic analyses of patient datasets compared TGF-β and PCNA expression in metastatic vs. normal tissues, and their association with survival. Mice with allergic inflammation showed increased lung metastases associated with TGF-β production. In patient samples, both TGF-β and PCNA were upregulated in metastatic tissues and correlated with poor overall survival. PCNA was also linked to genes involved in cell proliferation, DNA replication, and repair. Our results show an association between allergic airway inflammation and extensive lung metastasis of osteosarcoma in a comorbidity mouse model with elevated expression of TGF-β and PCNA.