Circulating extracellular vesicle-associated TGFß3 modulates response to cytotoxic therapy in head and neck squamous cell carcinoma.
Carcinogenesis
; 40(12): 1452-1461, 2019 Dec 31.
Article
em En
| MEDLINE
| ID: mdl-31436806
ABSTRACT
Management of locally advanced head and neck squamous cell carcinoma (HNSCC) requires a multi-prong approach comprising surgery, radiation and/or chemotherapy, yet outcomes are limited. This is largely due to a paucity of biomarkers that can predict response to specific treatment modalities. Here, we evaluated TGFß3 protein levels in extracellular vesicles (EVs) released by HNSCC cells as a predictor for response to chemoradiation therapy (CRT). To this end, specific EV-fractions were isolated from cell lines or HNSCC patient plasma, and TGFß3 protein was quantified. In patients treated with CRT, TGFß3 levels were found to be significantly higher in plasma EV-fractions or non-responders compared with responders. High levels of TGFß3 levels in Annexin V-EVs were associated with the worst progression-free survival. In vitro experiments demonstrated that TGFß3 silencing sensitized HNSCC cells to cytotoxic therapies, and this phenotype could be rescued by treatment with exogenous. In addition, specific EV-fractions shed by cisplatin-resistant cells were sufficient to transfer the resistant phenotype to sensitive cells through activation of TGFß-signaling pathway. Therefore, our data show that TGFß3 transmitted through EV plays a significant role in response to cytotoxic therapy, which can be exploited as a potential biomarker for CRT response in HNSCC patients treated with curative intent.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Biomarcadores Tumorais
/
Fator de Crescimento Transformador beta3
/
Vesículas Extracelulares
/
Carcinoma de Células Escamosas de Cabeça e Pescoço
/
Neoplasias de Cabeça e Pescoço
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Brasil