Elucidating the Association Between the Upregulation of Angiotensin Type 1-Receptors and the Development of Gastrointest
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REVIEW ARTICLE
Elucidating the Association Between the Upregulation of Angiotensin Type 1-Receptors and the Development of Gastrointestinal Malignancies Mohammad-Hassan Arjmand 1,2 Accepted: 2 November 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract The renin-angiotensin system (RAS) is a major regulator of body fluid hemostasis and blood pressure. Angiotensin type 1 receptors (AT1R) are one of the major components of this system and are widely expressed in different organs, including the gastrointestinal (GI) system. Very little known about the physiological roles of AT1R in GI tract but evidence has reported that local AT1Rs are upregulated in pathological conditions like GI malignancies and play role in stimulation of signaling pathways associated with GI cancers progression. AT1Rs axes signaling in tumor microenvironments stimulate inflammation and facilitate vascularization around the tumor cell to display invasive behavior. AT1Rs in stroma cells promote tumor-associated angiogenesis by upregulated of vessel endothelial growth factor (VEGF). Also, AT1Rs by the activation of molecular mechanisms such as PI3/Akt/NF-κB pathways increase the invasion of tumor cells. Experimental and clinical studies have reported that AT1R antagonists have beneficial influences by increasing the survival of patients with GI malignancies and reduction in the proliferation of GI cancer cell lines in vitro, and the growth and metastasis of tumors in vivo, therefore, AT1Rs antagonist have the potential for future anticancer strategies. This review focuses on the pathological roles of AT1Rs in GI malignancies. Keywords Angiotensin type1 receptor . Gastrointestinal cancer . Tumor microenvironment . Angiogenesis . Tumor growth
Abbreviations AngII Angiotensin II RAS Renin angiotensin system AT1R Angiotensin type 1 receptor ACE Angiotensin convert enzyme COX-2 Cyclooxygenase-2 EGFR Epithermal growth factor receptor FGF Fibroblast growth factor GI Gastrointestinal HIF1α hypoxia inducible factor 1α MAPK Mitogen activation protein kinase NF-kB Nuclear factor kappa B PKC Protein kinase C TAMs Tumor-associated macrophages * Mohammad-Hassan Arjmand [email protected] 1
Medical Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran
2
Cancer Research Center, Shahrekord University of Medical Sciences, Shahrekord, Iran
PDGF PKB PPARγ VEGF
Platelet-derived growth factor Protein kinase B Peroxisome proliferator–activated receptor γ Vessel endothelial growth factor
Introduction Renin angiotensin system (RAS) is an endocrine system with different peptides that release in the systemic circulation to regard blood pressure hemostasis and act on target organs. Angiotensin type 1 receptor (AT1R), as G protein–coupled receptors, is one of main receptor of RAS system that mediates intracellular signaling pathways of angiotensin II (AngII) when binding to AngII. AngII is an octapeptide that produced with function of angiotensin convert enzyme (ACE) by cle
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