Clinical Relevance of Increased Endothelial and Mesothelial Expression of Proangiogenic Proteases and VEGFA in the Omentum of Patients with Metastatic Ovarian High-Grade Serous Carcinoma

2.50
Hdl Handle:
http://hdl.handle.net/11287/593837
Title:
Clinical Relevance of Increased Endothelial and Mesothelial Expression of Proangiogenic Proteases and VEGFA in the Omentum of Patients with Metastatic Ovarian High-Grade Serous Carcinoma
Authors:
Winiarski, B. K.; Cope, Nichola; Alexander, M.; Pilling, L. C.; Warren, S.; Acheson, Nigel; Gutowski, Nicholas J.; Whatmore, Jacqueline L.
Abstract:
Epithelial ovarian cancer (EOC) metastasis to the omentum requires implantation and angiogenesis. We propose that prometastatic changes in the omental endothelium (for angiogenesis) and mesothelium (for implantation) are critical. We investigated the expression of angiogenic proteases [cathepsin D (CD), cathepsin L (CL), and matrix metalloproteinase 2 (MMP2) and MMP9] and vascular endothelial growth factor A (VEGFA) in the mesothelium and endothelium of omentum from patients with EOC with omental metastases and control patients with benign ovarian tumors. Endothelial expression of CL, VEGFA, and MMP9 and mesothelial expression of VEGFA, MMP9, and CD were significantly increased in patients with metastasized EOC. High expression of MMP9 and VEGFA in endothelium and mesothelium and CD in mesothelium was positively associated with poor disease-specific survival (DSS). High MMP9 expression in either endothelium or mesothelium and presence of ascites prospectively showed the greatest risk of shorter DSS [hazard ratio (HR)= 6.16, 95% confidence interval (CI) = 1.76-21.6, P = .0045; HR = 11.42, 95% CI = 2.59-50.35, P = .0013; and HR = 6.35, 95% CI = 2.01-20.1, P = .002, respectively]. High endothelial MMP9 expression and ascites were independent predictors of reduced DSS and overall survival, together resulting in worst patient prognosis. Our data show that omental metastasis of EOC is associated with increased proangiogenic protein expression in the omental endothelium and mesothelium.
Citation:
Transl Oncol. 2014 Apr;7(2):267-276.
Publisher:
Wiley
Journal:
Translational oncology
Issue Date:
1-Apr-2014
URI:
http://hdl.handle.net/11287/593837
DOI:
10.1016/j.tranon.2014.02.013
PubMed ID:
24913675
Additional Links:
http://linkinghub.elsevier.com/retrieve/pii/S1936-5233(14)00014-X
Note:
This article is available via Open Access. Please click on the 'Additional Link' above to access the full-text.
Type:
Journal Article
Language:
eng
ISSN:
1936-5233
Appears in Collections:
Neurology; 2014 RD&E publications; Oncology; Honorary contracts publications

Full metadata record

DC FieldValue Language
dc.contributor.authorWiniarski, B. K.en
dc.contributor.authorCope, Nicholaen
dc.contributor.authorAlexander, M.en
dc.contributor.authorPilling, L. C.en
dc.contributor.authorWarren, S.en
dc.contributor.authorAcheson, Nigelen
dc.contributor.authorGutowski, Nicholas J.en
dc.contributor.authorWhatmore, Jacqueline L.en
dc.date.accessioned2016-01-19T12:35:35Zen
dc.date.available2016-01-19T12:35:35Zen
dc.date.issued2014-04-01en
dc.identifier.citationTransl Oncol. 2014 Apr;7(2):267-276.en
dc.identifier.issn1936-5233en
dc.identifier.pmid24913675en
dc.identifier.doi10.1016/j.tranon.2014.02.013en
dc.identifier.urihttp://hdl.handle.net/11287/593837en
dc.description.abstractEpithelial ovarian cancer (EOC) metastasis to the omentum requires implantation and angiogenesis. We propose that prometastatic changes in the omental endothelium (for angiogenesis) and mesothelium (for implantation) are critical. We investigated the expression of angiogenic proteases [cathepsin D (CD), cathepsin L (CL), and matrix metalloproteinase 2 (MMP2) and MMP9] and vascular endothelial growth factor A (VEGFA) in the mesothelium and endothelium of omentum from patients with EOC with omental metastases and control patients with benign ovarian tumors. Endothelial expression of CL, VEGFA, and MMP9 and mesothelial expression of VEGFA, MMP9, and CD were significantly increased in patients with metastasized EOC. High expression of MMP9 and VEGFA in endothelium and mesothelium and CD in mesothelium was positively associated with poor disease-specific survival (DSS). High MMP9 expression in either endothelium or mesothelium and presence of ascites prospectively showed the greatest risk of shorter DSS [hazard ratio (HR)= 6.16, 95% confidence interval (CI) = 1.76-21.6, P = .0045; HR = 11.42, 95% CI = 2.59-50.35, P = .0013; and HR = 6.35, 95% CI = 2.01-20.1, P = .002, respectively]. High endothelial MMP9 expression and ascites were independent predictors of reduced DSS and overall survival, together resulting in worst patient prognosis. Our data show that omental metastasis of EOC is associated with increased proangiogenic protein expression in the omental endothelium and mesothelium.en
dc.language.isoengen
dc.publisherWileyen
dc.relation.urlhttp://linkinghub.elsevier.com/retrieve/pii/S1936-5233(14)00014-Xen
dc.titleClinical Relevance of Increased Endothelial and Mesothelial Expression of Proangiogenic Proteases and VEGFA in the Omentum of Patients with Metastatic Ovarian High-Grade Serous Carcinomaen
dc.typeJournal Articleen
dc.identifier.journalTranslational oncologyen
dc.description.noteThis article is available via Open Access. Please click on the 'Additional Link' above to access the full-text.en

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