Platelets promote invasion and induce epithelial to mesenchymal transition in ovarian cancer cells by TGF-β signaling pathway

To test whether platelets could increase invasion potential and initiate EMT in ovarian cancer cells via a TGF-β signaling pathway. 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 w...

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Veröffentlicht in:Gynecologic oncology Jg. 153; H. 3; S. 639 - 650
Hauptverfasser: Guo, Yi, Cui, Wei, Pei, Yuqing, Xu, Danfei
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States Elsevier Inc 01.06.2019
Schlagworte:
A83–01
Adult
Animals
Blood Platelets
Cadherins - genetics
Cadherins - metabolism
Cell Line, Tumor
Cell Movement - drug effects
Coculture Techniques
Epithelial to mesenchymal transition
Epithelial-Mesenchymal Transition - genetics
Female
Fibronectins - genetics
Gene Expression
Healthy Volunteers
Humans
Matrix Metalloproteinase 2 - genetics
Matrix Metalloproteinase 2 - metabolism
Mice
Middle Aged
Neoplasm Invasiveness
Neoplasm Transplantation
Ovarian cancer
Ovarian Neoplasms - blood
Ovarian Neoplasms - pathology
Platelet
Platelet Count
Pyrazoles - pharmacology
Receptor, Transforming Growth Factor-beta Type I - antagonists & inhibitors
Signal Transduction
Smad Proteins - metabolism
Snail Family Transcription Factors - genetics
TGF-β
Thiosemicarbazones - pharmacology
Transforming Growth Factor beta - blood
Transforming Growth Factor beta - metabolism
Up-Regulation
Vimentin - genetics
Epithelial to mesenchymal transition
TGF-β
Platelet
A83–01
Ovarian cancer
ISSN:0090-8258, 1095-6859, 1095-6859
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Zusammenfassung:To test whether platelets could increase invasion potential and initiate EMT in ovarian cancer cells via a TGF-β signaling pathway. 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-β pathway was examined by ELISA and Western blotting. TGF-β type I receptor (TβR I) inhibitor A83-01 was used to confirm the role of TGF-β pathway in vitro and in vivo. 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-β level was observed in patients with elevated platelet counts when compared to the subjects. Higher levels of TGF-β were also found in culture medium treated with platelets, and cells treated with platelets also showed increased phosphorylation of Smad2. TβR I inhibitor A83–01 reversed the EMT-like alterations and inhibited platelet-induced invasion in vitro and in vivo. Platelet increased invasion potential and induced EMT in ovarian cancer cells in a TGF-β dependent pathway. Platelet-derived TGF-β may be useful as a new target treatment for ovarian cancer. •Ovarian cancer patients with elevated platelets showed higher incidence of metastasis.•Platelets increase invasive ability and induce EMT in ovarian cancer cells.•Serum TGF-β level was higher in ovarian cancer patients with elevated platelet.•TGF-β/Smad pathway was activated in platelet-treated ovarian cancer cells.•TGF-β type I receptor inhibitor A83-01 abolished platelets-induced invasion and EMT in vitro and in vivo.
Bibliographie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:0090-8258
1095-6859
1095-6859
DOI:10.1016/j.ygyno.2019.02.026