Platelets promote invasion and induce epithelial to mesenchymal transition in ovarian cancer cells by TGF-ß signaling pathway.
Gynecol Oncol
; 153(3): 639-650, 2019 06.
Article
em En
| MEDLINE
| ID: mdl-30928020
ABSTRACT
OBJECTIVE:
To test whether platelets could increase invasion potential and initiate EMT in ovarian cancer cells via a TGF-ß signaling pathway.METHODS:
Blood samples were collected in 69 patients with ovarian cancer, 16 patients with benign ovarian tumor and 64 healthy donors. SK-OV-3 and OVCAR-3 ovarian cancer cells were treated with platelets. Transwell assays were used to analyze the invasive capacity, and EMT was assessed by microarray analysis, quantitative real-time PCR (qPCR) and Western blotting. Activation of TGF-ß pathway was examined by ELISA and Western blotting. TGF-ß type I receptor (TßR I) inhibitor A83-01 was used to confirm the role of TGF-ß pathway in vitro and in vivo.RESULTS:
Clinical data showed ovarian cancer patients with elevated platelet counts had a higher incidence of advanced stages. Treatment with platelets increased the invasive properties of both cell lines. Mesenchymal markers (snail family transcriptional repressor-1, vimentin, neural cadherin, fibronectin-1 and matrix metalloproteinase-2) were up-regulated in platelet-treated cells, while the epithelial marker (epithelial cadherin) was down-regulated. Higher TGF-ß level was observed in patients with elevated platelet counts when compared to the subjects. Higher levels of TGF-ß were also found in culture medium treated with platelets, and cells treated with platelets also showed increased phosphorylation of Smad2. TßR I inhibitor A83-01 reversed the EMT-like alterations and inhibited platelet-induced invasion in vitro and in vivo.CONCLUSION:
Platelet increased invasion potential and induced EMT in ovarian cancer cells in a TGF-ß dependent pathway. Platelet-derived TGF-ß may be useful as a new target treatment for ovarian cancer.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Ovarianas
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Plaquetas
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Fator de Crescimento Transformador beta
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Transição Epitelial-Mesenquimal
Limite:
Adult
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Animals
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Female
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Humans
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Middle aged
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article