Renin-angiotensin system and cancer: A review - 0 views
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crucial role of the RAS in the development and maintenance of cancer
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kidneys, which produce renin in response to decreased arterial pressure, reduced sodium in the distal tubule, or sympathetic nervous system activity via the β-adrenergic receptors
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Renin is secreted from the juxtaglomerular cells into the bloodstream where it encounters angiotensinogen (AGN), normally produced by the liver
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Renin catalyses the conversion of AGN to angiotensin I (ATI), which is quickly cleaved by angiotensin converting enzyme (ACE) to form angiotensin II (ATII)
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ATII triggers the release of aldosterone from the adrenal glands, which stimulates reabsorption of sodium and water and thereby increases blood volume and blood pressure
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ATII promotes the release of antidiuretic hormone from the posterior pituitary gland, which results in water retention and triggers the thirst reflex
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ability of non-CSCs to ‘de-differentiate’ into CSCs due to epigenetic or environmental factors, which further increases the complexity of tumour biology and treatment
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A localised (‘paracrine’) RAS mechanism has been identified in many types of cancers, and interruption of the control of the RAS is thought to be the basis for its role in cancer
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Components of the RAS are expressed by these CSCs, supporting the hypothesis of the presence of a ‘paracrine RAS’ in regulating these CSCs
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a study of GBM demonstrating overexpression of PRR coupled with the observation that inhibition of renin reduces cellular proliferation and promotes apoptosis
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suggest a crucial role for PRR activation on the proliferation of CSCs, possibly via Wnt/β-catenin signalling, leading to carcinogenesis.
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Angiotensin converting enzyme (ACE), also known as CD143, is the endothelial-bound peptidase which physiologically converts ATI to ATII
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results suggest that an overactive ACE promotes cancer growth and progression, and an inhibited or low-activity ACE may have cancer-protective effects
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When bound to ATII or ATIII it causes vasoconstriction by stimulating the release of vasopressin, reabsorption of water and sodium by promoting secretion of aldosterone and insulin, fibrosis, cellular growth and migration, pro-inflammation, glucose release from the liver, increased plasma triglyceride concentration, and reduced gluconeogenesis
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ATIIR1 is a G-protein-coupled receptor, with downstream signalling involved in vasodilation, hypertrophy and NF-κB activation leading to TNF-α and PAI-1 expression
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ATIIR1 has well-documented links with cancer, with one study demonstrating its overexpression in ~20% of breast cancer patients
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the effect of RAS dysregulation has been associated with increased VEGF expression and angiogenesis in cancers
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In ovarian and cervical cancer, ATIIR1 overexpression has been shown to be an indicator of tumour invasiveness
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administration of ATIIR1 blockers (ARBs) have been associated with reduced tumour size, reduction in tumour vascularisation, lower occurrence of metastases, and lower VEGF levels