TGFbeta carrying exosomes in plasma: potential biomarkers of cancer progression in patients with head and neck squamous cell carcinoma
Menée à l'aide d'un modèle murin de carcinogenèse, de données du projet "The Cancer Genome Atlas" ainsi que d'échantillons plasmatiques et tumoraux issus de patients atteints d'un carcinome épidermoïde de la tête et du cou, cette étude met en évidence une association entre le niveau du TGFbêta transporté par les exosomes circulants et la progression de la maladie
Objectives : Contributions of TGF
β to cancer progression are well documented. However, plasma TGFβ levels often do not correlate with clinicopathological data. We examine the role of TGFβ 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 methods
:
The 4-nitroquinoline-1-oxide (4-NQO) mouse model was used to study changes in TGFβ expression levels during oral carcinogenesis. In human HNSCC, TGFβ and Smad3 protein expression levels and TGFB1 gene expression were determined. Soluble TGFβ levels were evaluated by ELISA and TGFβ bioassays. Exosomes were isolated from plasma using size exclusion chromatography, and TGFβ content was quantified using bioassays and bioprinted microarrays.
Results
:
During 4-NQO carcinogenesis, TGFβ levels in tumour tissues and in serum increased as the tumour progressed. The TGFβ content of circulating exosomes also increased. In HNSCC patients, TGFβ, Smad3 and TGFB1 were overexpressed in tumour tissues and correlated with increased soluble TGFβ levels. Neither TGFβ expression in tumours nor levels of soluble TGFβ correlated with clinicopathological data or survival. Only exosome-associated TGFβ reflected tumour progression and correlated with tumour size.
Conclusions
:
Circulating TGFβ+ exosomes in the plasma of patients with HNSCC emerge as potential non-invasive biomarkers of disease progression in HNSCC.
British Journal of Cancer , résumé, 2023