Zusammenfassung
ObjectivesContributions of TGF beta to cancer progression are well documented. However, plasma TGF beta levels often do not correlate with clinicopathological data. We examine the role of TGF beta carried in exosomes isolated from murine and human plasma as a contributor to disease progression in head and neck squamous cell carcinoma (HNSCC).Materials and methodsThe 4-nitroquinoline-1-oxide ...
Zusammenfassung
ObjectivesContributions of TGF beta to cancer progression are well documented. However, plasma TGF beta levels often do not correlate with clinicopathological data. We examine the role of TGF beta carried in exosomes isolated from murine and human plasma as a contributor to disease progression in head and neck squamous cell carcinoma (HNSCC).Materials and methodsThe 4-nitroquinoline-1-oxide (4-NQO) mouse model was used to study changes in TGF beta expression levels during oral carcinogenesis. In human HNSCC, TGF beta and Smad3 protein expression levels and TGFB1 gene expression were determined. Soluble TGF beta levels were evaluated by ELISA and TGF beta bioassays. Exosomes were isolated from plasma using size exclusion chromatography, and TGF beta content was quantified using bioassays and bioprinted microarrays.ResultsDuring 4-NQO carcinogenesis, TGF beta levels in tumour tissues and in serum increased as the tumour progressed. The TGF beta content of circulating exosomes also increased. In HNSCC patients, TGF beta, Smad3 and TGFB1 were overexpressed in tumour tissues and correlated with increased soluble TGF beta levels. Neither TGF beta expression in tumours nor levels of soluble TGF beta correlated with clinicopathological data or survival. Only exosome-associated TGF beta reflected tumour progression and correlated with tumour size.ConclusionsCirculating TGF beta(+) exosomes in the plasma of patients with HNSCC emerge as potential non-invasive biomarkers of disease progression in HNSCC.