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Exenatide modulates tumor–endothelial cell interactions in human ovarian cancer cells

Diabetes and cancer are prevalent diseases whose incidence is increasing globally. Diabetic women have a moderate risk increase in ovarian cancer, suggested to be due to an interaction between these two disorders. Furthermore, patients manifesting both diseases have associated worse prognosis, reduc...

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Autores principales: Kosowska, Agnieszka, Gallego-Colon, Enrique, Garczorz, Wojciech, Kłych-Ratuszny, Agnieszka, Aghdam, Mohammad Reza F, Woz´niak, Michał, Witek, Andrzej, Wróblewska-Czech, Agnieszka, Cygal, Anna, Wojnar, Jerzy, Francuz, Tomasz
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Bioscientifica Ltd 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5682419/
https://www.ncbi.nlm.nih.gov/pubmed/29042458
http://dx.doi.org/10.1530/EC-17-0294
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author Kosowska, Agnieszka
Gallego-Colon, Enrique
Garczorz, Wojciech
Kłych-Ratuszny, Agnieszka
Aghdam, Mohammad Reza F
Woz´niak, Michał
Witek, Andrzej
Wróblewska-Czech, Agnieszka
Cygal, Anna
Wojnar, Jerzy
Francuz, Tomasz
author_facet Kosowska, Agnieszka
Gallego-Colon, Enrique
Garczorz, Wojciech
Kłych-Ratuszny, Agnieszka
Aghdam, Mohammad Reza F
Woz´niak, Michał
Witek, Andrzej
Wróblewska-Czech, Agnieszka
Cygal, Anna
Wojnar, Jerzy
Francuz, Tomasz
author_sort Kosowska, Agnieszka
collection PubMed
description Diabetes and cancer are prevalent diseases whose incidence is increasing globally. Diabetic women have a moderate risk increase in ovarian cancer, suggested to be due to an interaction between these two disorders. Furthermore, patients manifesting both diseases have associated worse prognosis, reduced survival and shorter relapse-free survival. According to current recommendations, incretin drugs such as Exenatide, a synthetic analog of Exendin-4, and Liraglutide are used as therapy for the type 2 diabetes (T2D). We studied the effects of GLP-1 and Exendin-4 on migration, apoptosis and metalloproteinase production in two human ovarian cancer cells (SKOV-3 and CAOV-3). Exendin-4 inhibited migration and promoted apoptosis through caspase 3/7 activation. Exendin-4 also modulated the expression of key metalloproteinases (MMP-2 and MMP-9) and their inhibitors (TIMP-1 and TIMP-2). Vascular endothelial cells, which contribute to the formation and progression of metastasis, were also analyzed. TNF-α-stimulated endothelial cells from iliac artery after Exendin-4 treatment showed reduced production of adhesion molecules (ICAM-1 and VCAM-1). Additionally, incretin treatment inhibited activation of apoptosis in TNF-α-stimulated endothelial cells. In the same experiment, MMPs (MMP-1 and MMP-9), which are relevant for tumor development, were also reduced. Our study demonstrated that incretin drugs may reduce cancer cell proliferation and dissemination potential, hence limiting the risk of metastasis in epithelial ovarian cancer.
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spelling pubmed-56824192017-11-16 Exenatide modulates tumor–endothelial cell interactions in human ovarian cancer cells Kosowska, Agnieszka Gallego-Colon, Enrique Garczorz, Wojciech Kłych-Ratuszny, Agnieszka Aghdam, Mohammad Reza F Woz´niak, Michał Witek, Andrzej Wróblewska-Czech, Agnieszka Cygal, Anna Wojnar, Jerzy Francuz, Tomasz Endocr Connect Research Diabetes and cancer are prevalent diseases whose incidence is increasing globally. Diabetic women have a moderate risk increase in ovarian cancer, suggested to be due to an interaction between these two disorders. Furthermore, patients manifesting both diseases have associated worse prognosis, reduced survival and shorter relapse-free survival. According to current recommendations, incretin drugs such as Exenatide, a synthetic analog of Exendin-4, and Liraglutide are used as therapy for the type 2 diabetes (T2D). We studied the effects of GLP-1 and Exendin-4 on migration, apoptosis and metalloproteinase production in two human ovarian cancer cells (SKOV-3 and CAOV-3). Exendin-4 inhibited migration and promoted apoptosis through caspase 3/7 activation. Exendin-4 also modulated the expression of key metalloproteinases (MMP-2 and MMP-9) and their inhibitors (TIMP-1 and TIMP-2). Vascular endothelial cells, which contribute to the formation and progression of metastasis, were also analyzed. TNF-α-stimulated endothelial cells from iliac artery after Exendin-4 treatment showed reduced production of adhesion molecules (ICAM-1 and VCAM-1). Additionally, incretin treatment inhibited activation of apoptosis in TNF-α-stimulated endothelial cells. In the same experiment, MMPs (MMP-1 and MMP-9), which are relevant for tumor development, were also reduced. Our study demonstrated that incretin drugs may reduce cancer cell proliferation and dissemination potential, hence limiting the risk of metastasis in epithelial ovarian cancer. Bioscientifica Ltd 2017-10-17 /pmc/articles/PMC5682419/ /pubmed/29042458 http://dx.doi.org/10.1530/EC-17-0294 Text en © 2017 The authors http://creativecommons.org/licenses/by-nc/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/) .
spellingShingle Research
Kosowska, Agnieszka
Gallego-Colon, Enrique
Garczorz, Wojciech
Kłych-Ratuszny, Agnieszka
Aghdam, Mohammad Reza F
Woz´niak, Michał
Witek, Andrzej
Wróblewska-Czech, Agnieszka
Cygal, Anna
Wojnar, Jerzy
Francuz, Tomasz
Exenatide modulates tumor–endothelial cell interactions in human ovarian cancer cells
title Exenatide modulates tumor–endothelial cell interactions in human ovarian cancer cells
title_full Exenatide modulates tumor–endothelial cell interactions in human ovarian cancer cells
title_fullStr Exenatide modulates tumor–endothelial cell interactions in human ovarian cancer cells
title_full_unstemmed Exenatide modulates tumor–endothelial cell interactions in human ovarian cancer cells
title_short Exenatide modulates tumor–endothelial cell interactions in human ovarian cancer cells
title_sort exenatide modulates tumor–endothelial cell interactions in human ovarian cancer cells
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5682419/
https://www.ncbi.nlm.nih.gov/pubmed/29042458
http://dx.doi.org/10.1530/EC-17-0294
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