TNF-α induces endothelial-mesenchymal transition promoting stromal development of pancreatic adenocarcinoma.
Cell Death Dis
; 12(7): 649, 2021 06 25.
Article
em En
| MEDLINE
| ID: mdl-34172716
ABSTRACT
Endothelial-mesenchymal transition (EndMT) is an important source of cancer-associated fibroblasts (CAFs), which facilitates tumour progression. PDAC is characterised by abundant CAFs and tumour necrosis factor-α (TNF-α). Here, we show that TNF-α strongly induces human endothelial cells to undergo EndMT. Interestingly, TNF-α strongly downregulates the expression of the endothelial receptor TIE1, and reciprocally TIE1 overexpression partially prevents TNF-α-induced EndMT, suggesting that TNF-α acts, at least partially, through TIE1 regulation in this process. We also show that TNF-α-induced EndMT is reversible. Furthermore, TNF-α treatment of orthotopic mice resulted in an important increase in the stroma, including CAFs. Finally, secretome analysis identified TNFSF12, as a regulator that is also present in PDAC patients. With the aim of restoring normal angiogenesis and better access to drugs, our results support the development of therapies targeting CAFs or inducing the EndMT reversion process in PDAC.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Pancreáticas
/
Fator de Necrose Tumoral alfa
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Carcinoma Ductal Pancreático
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Células Endoteliais
/
Transição Epitelial-Mesenquimal
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Fibroblastos Associados a Câncer
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Cell Death Dis
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
França