OBJECTIVE: To evaluate the role of VEGF-dependent Claudin 5 production for the development of ascites via influencing endothelial permeability in peritoneal tissue of ovarian cancer patients. METHODS: This study investigates the mechanisms of formation of ascites in ovarian cancer patients, performing RT-PCR, VEGF-ELISA and immunohistochemical dual staining for CD31 and Claudin 5. In addition, in order to analyze the connectivity of VEGF, Claudin 5, and endothelial permeability, an endothelial cell/ovarian cancer cell-co-culture-system was established and evaluated performing Western blot analysis and a permeability assay. RESULTS: Firstly, VEGF-gene expression was demonstrated for all ovarian cancer and peritoneal biopsies. In addition, quantification of VEGF in the serum and ascites of ovarian cancer patients revealed significantly increased values. We subsequently demonstrated Claudin 5 production in the peritoneal vessels, which was weaker than in the vessels of the controls. Evaluation of endothelial permeability finally showed a VEGF-dependent regulation via Claudin 5 suggesting a mechanism for the development of ascites in ovarian cancer patients. CONCLUSION: VEGF induces ascites in ovarian cancer patients. This instance happens due to increased peritoneal permeability, caused by downregulation of the tight junction protein Claudin 5 in the peritoneal endothelium.
OBJECTIVE: To evaluate the role of VEGF-dependent Claudin 5 production for the development of ascites via influencing endothelial permeability in peritoneal tissue of ovarian cancerpatients. METHODS: This study investigates the mechanisms of formation of ascites in ovarian cancerpatients, performing RT-PCR, VEGF-ELISA and immunohistochemical dual staining for CD31 and Claudin 5. In addition, in order to analyze the connectivity of VEGF, Claudin 5, and endothelial permeability, an endothelial cell/ovarian cancer cell-co-culture-system was established and evaluated performing Western blot analysis and a permeability assay. RESULTS: Firstly, VEGF-gene expression was demonstrated for all ovarian cancer and peritoneal biopsies. In addition, quantification of VEGF in the serum and ascites of ovarian cancerpatients revealed significantly increased values. We subsequently demonstrated Claudin 5 production in the peritoneal vessels, which was weaker than in the vessels of the controls. Evaluation of endothelial permeability finally showed a VEGF-dependent regulation via Claudin 5 suggesting a mechanism for the development of ascites in ovarian cancerpatients. CONCLUSION:VEGF induces ascites in ovarian cancerpatients. This instance happens due to increased peritoneal permeability, caused by downregulation of the tight junction protein Claudin 5 in the peritoneal endothelium.
Authors: Mateusz Bujko; Paulina Kober; Michal Mikula; Marcin Ligaj; Jerzy Ostrowski; Janusz Aleksander Siedlecki Journal: Oncol Lett Date: 2015-04-08 Impact factor: 2.967
Authors: Gregory D Conway; Marguerite S Buzza; Erik W Martin; Nadire Duru; Tierra A Johnson; Raymond J Peroutka; Nisha R Pawar; Toni M Antalis Journal: J Mol Med (Berl) Date: 2019-03-25 Impact factor: 4.599
Authors: James S Ferriss; James J Java; Michael A Bookman; Gini F Fleming; Bradley J Monk; Joan L Walker; Howard D Homesley; Jeffrey Fowler; Benjamin E Greer; Matthew P Boente; Robert A Burger Journal: Gynecol Oncol Date: 2015-07-26 Impact factor: 5.482