Assessment of serum angiotensin-converting enzyme in patients with epithelial ovarian cancer

Beyazıt, Fatma; Ayhan, Sevgi; Çelik, Hüseyin; Güngör, Tayfun

doi:10.1007/s00404-015-3661-x

Cited by 30 publications

(18 citation statements)

References 21 publications

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“…In addition, membrane-bound glycoproteins (including ACE) may often be shed into blood circulation as a by-product of the disease process. Recently an increase in blood ACE level was demonstrated for patients with epithelial ovarian carcinoma [ 50 ]. Likely, such an increase may be explained by an increase of local vascular permeability induced by the increased VEGF production by tumor tissues.…”

Section: Resultsmentioning

confidence: 99%

Tissue Specificity of Human Angiotensin I-Converting Enzyme

et al. 2015

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BackgroundAngiotensin-converting enzyme (ACE), which metabolizes many peptides and plays a key role in blood pressure regulation and vascular remodeling, as well as in reproductive functions, is expressed as a type-1 membrane glycoprotein on the surface of endothelial and epithelial cells. ACE also presents as a soluble form in biological fluids, among which seminal fluid being the richest in ACE content - 50-fold more than that in blood.Methods/Principal FindingsWe performed conformational fingerprinting of lung and seminal fluid ACEs using a set of monoclonal antibodies (mAbs) to 17 epitopes of human ACE and determined the effects of potential ACE-binding partners on mAbs binding to these two different ACEs. Patterns of mAbs binding to ACEs from lung and from seminal fluid dramatically differed, which reflects difference in the local conformations of these ACEs, likely due to different patterns of ACE glycosylation in the lung endothelial cells and epithelial cells of epididymis/prostate (source of seminal fluid ACE), confirmed by mass-spectrometry of ACEs tryptic digests.ConclusionsDramatic differences in the local conformations of seminal fluid and lung ACEs, as well as the effects of ACE-binding partners on mAbs binding to these ACEs, suggest different regulation of ACE functions and shedding from epithelial cells in epididymis and prostate and endothelial cells of lung capillaries. The differences in local conformation of ACE could be the base for the generation of mAbs distingushing tissue-specific ACEs.

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Section: Resultsmentioning

confidence: 99%

Tissue Specificity of Human Angiotensin I-Converting Enzyme

et al. 2015

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“…Angiotensin II (AngII) was initially discovered as a vasoconstrictor, but is also known to contribute to the formation of the ECM (15). In ovarian cancer patients, it has been shown that (i) the level of tumor fibrosis inversely correlates with recurrence-free survival and overall survival (16), (ii) the serum level of angiotensin-converting enzyme (ACE), which converts inactive angiotensin I to the bioactive AngII, is elevated (17), and (iii) AT1 expression is associated with poor patient outcome (18,19). Losartan is a Food and Drug Administration (FDA)-approved antihypertensive agent that blocks angiotensin II receptor type 1 (AT1).…”

Section: Significancementioning

confidence: 99%

Losartan treatment enhances chemotherapy efficacy and reduces ascites in ovarian cancer models by normalizing the tumor stroma

Zhao

Cao

Melamed

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

202

152

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In ovarian cancer patients, tumor fibrosis and angiotensin-driven fibrogenic signaling have been shown to inversely correlate with survival. We sought to enhance drug delivery and therapeutic efficacy by remodeling the dense extracellular matrix in two orthotopic human ovarian carcinoma xenograft models. We hypothesized that targeting the angiotensin signaling axis with losartan, an approved angiotensin system inhibitor, could reduce extracellular matrix content and the associated “solid stress,” leading to better anticancer therapeutic effect. We report here four translatable findings: (i) losartan treatment enhances the efficacy of paclitaxel—a drug used for ovarian cancer treatment—via normalizing the tumor microenvironment, resulting in improved vessel perfusion and drug delivery; (ii) losartan depletes matrix via inducing antifibrotic miRNAs that should be tested as candidate biomarkers of response or resistance to chemotherapy; (iii) although losartan therapy alone does not reduce tumor burden, it reduces both the incidence and the amount of ascites formed; and (iv) our retrospective analysis revealed that patients receiving angiotensin system inhibitors concurrently with standard treatment for ovarian cancer exhibited 30 mo longer overall survival compared with patients on other antihypertensives. Our findings provide the rationale and supporting data for a clinical trial on combined losartan and chemotherapy in ovarian cancer patients.

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“…ACE levels were significantly upregulated in patients with ovarian cancer. There was no correlation recognizable for FIGO stages or pathologic subtypes [ 12 ].…”

Section: Discussionmentioning

confidence: 99%

“…As there are studies proving that the activity of the RAS is increased in ovarian cancer patients, we decided to investigate also the cascade-starting receptor PRR. Such increased activity is characterised by, for example, angiotensin II type 1 receptor (AGTR1), which has a prognostic role in EOC [ 11 ], or angiotensin converting enzyme (ACE) which is upregulated in cancer patients [ 12 ]. The presence of a soluble form (sPRR) makes the receptor more likely to become an easy quantifiable marker.…”

Section: Introductionmentioning

confidence: 99%

Predictive and Prognostic Value of sPRR in Patients with Primary Epithelial Ovarian Cancer

Kreienbring

Franz

Richter

et al. 2016

Analytical Cellular Pathology

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Aim. The purpose of the present study was to analyze the predictive and prognostic role of soluble (pro)renin receptor (sPRR) as a biomarker for clinicopathological outcome in patients with primary epithelial ovarian cancer (EOC). As part of the renin-angiotensin system (RAS) whose activity is known to increase in ovarian cancer patients, the relation of sPRR and ovarian cancer should be further investigated. Patients and Methods. In this study 197 patients with primary EOC in our institution from 2000 to 2011 were included. sPRR was determined by enzyme-linked immunosorbent assay (ELISA) in preoperative taken blood sera. Associations with clinicopathological outcome were analyzed and serum levels of sPRR in patients have been compared to those in healthy specimen. Kaplan-Meier and logistic/Cox regression assessed the impact of the markers on progression-free survival (PFS) and overall survival (OS). Results. There have been no correlations proved of sPRR levels with neither clinicopathological factors nor prognostic data. Also the distribution of sPRR in patients and controls was normal. Conclusion. sPRR seems to have no predictive, prognostic, or diagnostic value in EOC. As several factors of the RAS which might indicate cancer events have been shown, sPRR seems not to be affected.

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Assessment of serum angiotensin-converting enzyme in patients with epithelial ovarian cancer

Cited by 30 publications

References 21 publications

Tissue Specificity of Human Angiotensin I-Converting Enzyme

Tissue Specificity of Human Angiotensin I-Converting Enzyme

Losartan treatment enhances chemotherapy efficacy and reduces ascites in ovarian cancer models by normalizing the tumor stroma

Predictive and Prognostic Value of sPRR in Patients with Primary Epithelial Ovarian Cancer

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