Thrombin promotes epithelial ovarian cancer cell invasion by inducing epithelial-mesenchymal transition / 부인종양
Journal of Gynecologic Oncology
;
: 265-272, 2013.
Artículo
en Inglés
| WPRIM
| ID: wpr-225934
ABSTRACT
OBJECTIVE:
Over-expression of thrombin in ovarian cancer cells is associated with poor prognosis. In this study, we investigated the role of thrombin in inducing epithelial-mesenchymal transition (EMT) in SKOV3 epithelial ovarian cancer cells.METHODS:
After thrombin treatment SKOV3 cells were subjected to western blots, reverse-transcription PCR, and enzyme-linked immunosorbent assay to quantify EMT-related proteins, mRNA expression of SMAD2, DKK1, and sFRP1, and the secretion of matrix metalloproteinases (MMPs) and cytokines. Meanwhile, invasion ability was evaluated using transwell assays.RESULTS:
The results indicated a dose- and time-dependent down-regulation of E-cadherin and upregulation of N-cadherin and vimentin in thrombin-treated SKOV3 cells, compared with the thrombin-free control group (p<0.05). There was a dose- and time-dependent increase in the levels of SMAD2 and DKK1 mRNAs and a decrease in the levels of sFRP1 mRNA in thrombin-treated SKOV3 cells compared to control cells (p<0.05). Thrombin-treated SKOV3 cells exhibited increased secretion of MMP-9, MMP-2, interleukin (IL)-8, and IL-6 and increased invasion compared to untreated cells (p<0.05). Thrombin altered the morphology of SKOV3 cells to a spindle-like phenotype. Addition of hirudin to thrombin-treated cells reversed the effects of thrombin.CONCLUSION:
Thrombin induced EMT and promoted the invasion of SKOV3 cells, possibly via distinct signaling pathways. Hirudin inhibited the effects of thrombin, suggesting that anticoagulant therapy could be a novel therapeutic strategy for ovarian carcinoma.
Texto completo:
Disponible
Índice:
WPRIM (Pacífico Occidental)
Asunto principal:
Neoplasias Ováricas
/
Fenotipo
/
Pronóstico
/
Vimentina
/
ARN Mensajero
/
Ensayo de Inmunoadsorción Enzimática
/
Trombina
/
Proteínas
/
Cadherinas
/
Regulación hacia Abajo
Tipo de estudio:
Estudio pronóstico
Idioma:
Inglés
Revista:
Journal of Gynecologic Oncology
Año:
2013
Tipo del documento:
Artículo
Similares
MEDLINE
...
LILACS
LIS