Abstract:Background: The (pro) renin receptor ((P)RR) plays important roles in various pathways, such as the Wnt/β-catenin, renin-angiotensin system (RAS), MAPK/ERK and PI3K/AKT/mTOR pathways, that are involved in a wide range of physiological and pathological processes incorporating the tumorigenesis. However, our knowledge about (P) RR was mostly limited to its roles in cardiovascular and renal physiological functions and diseases. In the past 5 years, however, compelling evidence has revealed that (P) RR is aberrant… Show more
“…Besides this, the staining of this protein was more intense in CCRCCs with high histological grade, diameter and stage, and was associated with a higher risk of mortality according to the UISS scale. These results agree with studies carried out in other solid tumours, showing the potential of PRR as a biomarker of worse prognosis [21]. Furthermore, we reported recently that PRR staining was not very different in the centre and front of colorectal cancers [27], a result that was repeated in RCCs.…”
Section: Discussionsupporting
confidence: 92%
“…The mechanism by which PRR upregulation could affect the progression of kidney could be RAS-dependent or -independent [12,21]. It is known that under pathologic conditions, PRR induces AngII/AT1R-dependent secretion of pro-fibrotic and pro-inflammatory cytokines in cells from the proximal and distal nephron [12].…”
Section: Discussionmentioning
confidence: 99%
“…PRR binds renin enzyme and its inactive precursor prorenin, which enhances their activity and the production of angiotensin I, which is converted by ACE in angiotensin II, leading to AT1R-mediated signals. PRR is also activated after the binding of (pro)renin, which leads to PI3/AKT/mTOR and MAPK/ERK signalling [12,20,21]. Besides this, PRR is considered to function as a hinge molecule between the Wnt receptor and the V-ATPase that mediates Wnt receptor internalization and the subsequent Wnt/β-catenin signaling [12,21].…”
Section: Introductionmentioning
confidence: 99%
“…These RAS-dependent and -independent signalling pathways contribute to cancer initiation, so it was expected that PRR expression could be altered in tumour tissues [21]. Thus, increases in this protein have been described in pancreatic ductal adenocarcinoma [22,23], glioma [24,25], colorectal [26,27], breast [28] and endometrial cancer [29].…”
Section: Introductionmentioning
confidence: 99%
“…Taking into account that PRR exerts important functions in kidney physiology and that it takes part in inflammatory and fibrotic processes of this organ [12], changes in this protein can also be expected in kidney neoplasms. The Cancer Genome Atlas (TCGA) described high mRNA levels of PRR in RCCs when compared with the uninvolved part of the kidney [21]. The Human Protein Atlas (https://www.proteinatlas.org) described PRR staining in RCCs; however, the analyses were limited to only 11 cases, which was insufficient to understand the association between this protein and tumour progression.…”
(1) Background: Renal cancer is one of the most frequent malignancies in Western countries, with an unpredictable clinical outcome, partly due to its high heterogeneity and the scarcity of reliable biomarkers of tumour progression. (Pro)renin receptor (PRR) is a novel receptor of the renin–angiotensin system (RAS) that has been associated with the development and progression of some solid tumours by RAS-dependent and -independent mechanisms. (2) Methods: In this study, we analysed the immunohistochemical expression of PRR at the centre and border in a series of 83 clear-cell renal cell (CCRCCs), 19 papillary (PRCC) and 7 chromophobe (ChRCC) renal cell carcinomas, and the benign tumour renal oncocytoma (RO, n = 11). (3) Results: PRR is expressed in all the tumour subtypes, with higher mean staining intensity in ChRCCs and ROs. A high expression of PRR at the tumour centre and at the infiltrative front of CCRCC tissues is significantly associated with high grade, tumour diameter, local invasion and stage, and with high mortality risk by UCLA integrated staging system (UISS) scale. (4) Conclusions: These findings indicate that PRR is associated with the development and progression of renal tumours. Its potential as a novel biomarker for RCC diagnosis/prognosis and as a promising therapeutic target should be taken into account in the future.
“…Besides this, the staining of this protein was more intense in CCRCCs with high histological grade, diameter and stage, and was associated with a higher risk of mortality according to the UISS scale. These results agree with studies carried out in other solid tumours, showing the potential of PRR as a biomarker of worse prognosis [21]. Furthermore, we reported recently that PRR staining was not very different in the centre and front of colorectal cancers [27], a result that was repeated in RCCs.…”
Section: Discussionsupporting
confidence: 92%
“…The mechanism by which PRR upregulation could affect the progression of kidney could be RAS-dependent or -independent [12,21]. It is known that under pathologic conditions, PRR induces AngII/AT1R-dependent secretion of pro-fibrotic and pro-inflammatory cytokines in cells from the proximal and distal nephron [12].…”
Section: Discussionmentioning
confidence: 99%
“…PRR binds renin enzyme and its inactive precursor prorenin, which enhances their activity and the production of angiotensin I, which is converted by ACE in angiotensin II, leading to AT1R-mediated signals. PRR is also activated after the binding of (pro)renin, which leads to PI3/AKT/mTOR and MAPK/ERK signalling [12,20,21]. Besides this, PRR is considered to function as a hinge molecule between the Wnt receptor and the V-ATPase that mediates Wnt receptor internalization and the subsequent Wnt/β-catenin signaling [12,21].…”
Section: Introductionmentioning
confidence: 99%
“…These RAS-dependent and -independent signalling pathways contribute to cancer initiation, so it was expected that PRR expression could be altered in tumour tissues [21]. Thus, increases in this protein have been described in pancreatic ductal adenocarcinoma [22,23], glioma [24,25], colorectal [26,27], breast [28] and endometrial cancer [29].…”
Section: Introductionmentioning
confidence: 99%
“…Taking into account that PRR exerts important functions in kidney physiology and that it takes part in inflammatory and fibrotic processes of this organ [12], changes in this protein can also be expected in kidney neoplasms. The Cancer Genome Atlas (TCGA) described high mRNA levels of PRR in RCCs when compared with the uninvolved part of the kidney [21]. The Human Protein Atlas (https://www.proteinatlas.org) described PRR staining in RCCs; however, the analyses were limited to only 11 cases, which was insufficient to understand the association between this protein and tumour progression.…”
(1) Background: Renal cancer is one of the most frequent malignancies in Western countries, with an unpredictable clinical outcome, partly due to its high heterogeneity and the scarcity of reliable biomarkers of tumour progression. (Pro)renin receptor (PRR) is a novel receptor of the renin–angiotensin system (RAS) that has been associated with the development and progression of some solid tumours by RAS-dependent and -independent mechanisms. (2) Methods: In this study, we analysed the immunohistochemical expression of PRR at the centre and border in a series of 83 clear-cell renal cell (CCRCCs), 19 papillary (PRCC) and 7 chromophobe (ChRCC) renal cell carcinomas, and the benign tumour renal oncocytoma (RO, n = 11). (3) Results: PRR is expressed in all the tumour subtypes, with higher mean staining intensity in ChRCCs and ROs. A high expression of PRR at the tumour centre and at the infiltrative front of CCRCC tissues is significantly associated with high grade, tumour diameter, local invasion and stage, and with high mortality risk by UCLA integrated staging system (UISS) scale. (4) Conclusions: These findings indicate that PRR is associated with the development and progression of renal tumours. Its potential as a novel biomarker for RCC diagnosis/prognosis and as a promising therapeutic target should be taken into account in the future.
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