Impact of renin‐angiotensin system blockade on clinical outcome in glioblastoma

Januel, Edouard; Ursu, Rénata; Alkhafaji, Adnan Taan; Marantidou, Athina; Doridam, Jennifer; Belin, Cathérine; Lévy-Piedbois, C.; Carpentier, Alexandre

doi:10.1111/ene.12746

Cited by 33 publications

(20 citation statements)

References 30 publications

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“…Blockade of the RAS leads to inhibited growth of colorectal cancer liver metastases in the regenerating liver [33] and recent reports of increased overall survival of GB patients treated with angiotensin receptor blockers [34] , support the role of the RAS in cancer. It is exciting to speculate that CSCs in MM to the brain maybe a novel therapeutic target by modulating the RAS, although more work including a larger sample size, control tissue samples and in vitro and in vivo functional work is needed to determine the precise role of the RAS in this aggressive cancer.…”

Section: Discussionmentioning

confidence: 85%

Cancer stem cell subpopulations in metastatic melanoma to the brain express components of the renin-angiotensin system

Wickremesekera¹,

Brasch²,

Lee³

et al. 2019

JCMT

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Aim: There is increasing appreciation of the role of the renin-angiotensin system (RAS) in carcinogenesis with recent evidence showing expression of the RAS by cancer stem cells (CSCs) in different types of cancer. We have recently demonstrated the presence of three CSC subpopulations within metastatic melanoma (MM) to the brain: a Melan-A + subpopulation and a Melan-Asubpopulation within the tumor that express OCT4, SALL4, SOX2 and NANOG; and a pSTAT3 + subpopulation localized to the CD34 + endothelium of microvessels within the tumor. In this study we investigated the expression and localization of components of the RAS in relation to these CSCs in MM to the brain.Methods: 3, 3-diaminobenzidine immunohistochemical (IHC) staining of components of the RAS: pro-renin receptor (PRR), angiotensin converting enzyme (ACE), angiotensin II receptor 1 (ATIIR1) and angiotensin II receptor 2 (ATIIR2) was performed on the same ten samples of MM to the brain included in our previous study. Immunofluorescence IHC staining of these components of the RAS was performed with embryonic stem cell markers OCT4 and NANOG, and endothelial marker CD34, on two of the samples of MM to the brain from the original cohort of ten patients. Western blotting (n = 5) and NanoString mRNA analysis (n = 4) were performed on samples of MM to the brain to confirm protein and mRNA expression of these components of the RAS, respectively.Results: DAB IHC staining showed the presence of PRR, ACE, ATIIR1 and ATIIR2 in all ten samples of MM to the brain. IF IHC staining showed that the CSC subpopulations in MM to the brain expressed PRR, ATIIR1 and ATIIR2; and a CSC subpopulation on the endothelium of the microvessels expressed ACE. Western blotting and NanoString mRNA analysis confirmed protein and mRNA expression of these components of the RAS, respectively. Conclusion:CSCs in MM to the brain expressed components of the RAS. Targeting the CSCs using modulators of the RAS may be a novel therapeutic approach for treating this aggressive cancer.

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Section: Discussionmentioning

confidence: 85%

Cancer stem cell subpopulations in metastatic melanoma to the brain express components of the renin-angiotensin system

Wickremesekera¹,

Brasch²,

Lee³

et al. 2019

JCMT

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“…shown that selective synthetic renin inhibitors decrease DNA synthesis and induce apoptosis in GB cells (Juillerat-Jeanneret, Celerier et al 2004), and that ARBs are associated with statistically improved progression-free survival and overall survival in 81 patients with GB (Januel, Ursu et al 2015).…”

Section: Repurposing Drugs That Target the Rasmentioning

confidence: 99%

Therapeutic Targeting of Cancer Stem Cells in Human Glioblastoma by Manipulating the Renin-angiotensin System

Tan¹,

Roth²,

Wickremesekera³

et al. 2019

Preprint

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Patients with glioblastoma (GB), a highly aggressive brain tumor, have a median survival of 14.6 months following neurosurgical resection with adjuvant chemoradiotherapy. Quiescent GB cancer stem cells (CSCs) invariably cause local recurrence. These GB CSCs that can be identified by embryonic stem cell markers express components of the renin-angiotensin system and are associated with circulating CSCs. Despite the presence of circulating CSCs, GB rarely develops distant metastasis outside the central nervous system. This paper reviews the current literature on GB growth inhibition in relation to CSCs, circulating CSCs, the RAS and the novel therapeutic approach by repurposing drugs that target the renin-angiotensin system to improve overall symptom-free survival and maintain quality of life.

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“…Local RAS plays a pivotal role for the tissue function both physiologic and pathophysiologic conditions based on paracrine and autocrine impacts of it [26]. RAS also modulate the body metabolic process [18].…”

Section: The Function Of Local Renin-angiotensin Systems In the Livermentioning

confidence: 99%

Local Renin-Angiotensin System at Liver and Crosstalk with Hepatic Diseases

Taşkın¹,

Güven²

2017

Renin-Angiotensin System - Past, Present and Future

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The systemic renin-angiotensin system mainly regulates blood pressure and maintains kidney function. Recent studies have realized that renin-angiotensin system (RAS) has been found in many tissues, such as heart, liver, and kidney. Although RAS in heart and kidney has been well documented, the RAS in the liver has been evaluated in a few studies. Therefore, this chapter will be assessed it. Based on findings, RAS in the liver has presented almost all of its components, such as angiotensin-I (Ang-I), angiotensin-II (Ang-II), angiotensin-converting enzyme (ACE), angiotensin type-1 receptor (AT1), angiotensin type-2 receptor (AT2), named as classical RAS. Expect these components, the local RAS has had alternative pathway components, including angiotensin-converting enzyme 2 (ACE2) and chymase. Classical RAS has an opposite effect of alternative RAS.Although these local RAS might not be such a crucial for the tissue, it could be a more vital function under pathophysiologic conditions. The chapter the local RAS in the liver the under both physiologic and pathophysiologic conditions is highlighted.

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Impact of renin‐angiotensin system blockade on clinical outcome in glioblastoma

Abstract: Treatment with Ang-II inhibitors in combination with RT and TMZ might improve clinical outcome in GBMs. Prospective trials are needed to test this hypothesis.

Cited by 33 publications

References 30 publications

Cancer stem cell subpopulations in metastatic melanoma to the brain express components of the renin-angiotensin system

Cancer stem cell subpopulations in metastatic melanoma to the brain express components of the renin-angiotensin system

Therapeutic Targeting of Cancer Stem Cells in Human Glioblastoma by Manipulating the Renin-angiotensin System

Local Renin-Angiotensin System at Liver and Crosstalk with Hepatic Diseases

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