Mechanisms linking the renin-angiotensin system, obesity, and breast cancer

• Published in: Endocrine-related cancer Vol. 26; no. 12; pp. R653 - R672
• Main Authors: Rasha, Fahmida, Ramalingam, Latha, Gollahon, Lauren, Rahman, Rakshanda Layeequr, Rahman, Shaikh Mizanoor, Menikdiwela, Kalhara, Moustaid-Moussa, Naima
• Format: Journal Article
• Language: English
• Published: England Bioscientifica Ltd 01.12.2019; Society for Endocrinology & BioScientifica Ltd
• Subjects: ACE inhibitors; Adipose tissue; Angiotensin; Angiotensin II; Angiotensin-converting enzyme inhibitors; Antihypertensives; Breast cancer; Breast Neoplasms - complications; Breast Neoplasms - etiology; Breast Neoplasms - pathology; Cytokines; Female; Growth factors; Humans; Inflammation; Menopause; Obesity; Obesity - complications; Obesity - etiology; Obesity - pathology; Peptidyl-dipeptidase A; Renin; Renin-Angiotensin System - genetics; Review; Risk factors; breast cancer; adipose tissue inflammation; obesity; renin-angiotensin system
• ISSN: 1351-0088; 1479-6821; 1479-6821
• DOI: 10.1530/ERC-19-0314

Obesity is a complex disease and a global epidemic. It is a risk factor for other chronic diseases including breast cancer, especially in women after menopause. Diverse etiologies underlie the relationship between obesity and breast cancer. Adipose tissue is in part responsible for these interactions. In obesity, adipose tissue undergoes several metabolic dysregulations resulting in the secretion of many pro-inflammatory cytokines, growth factors, and hormones which in turn, can promote tumor microenvironment (TME) formation and cancer progression within the breast tissue. Angiotensin II (Ang II) is a well-known hypertensive hormone produced systemically and locally by the renin-angiotensin system (RAS). Activation of this system in obesity is a potential contributor to local and systemic inflammation in breast adipose tissue. Ang II actions are primarily mediated through binding to its two receptors, type 1 (AT1R) and type 2 (AT2R). RAS inhibitors include angiotensin-converting enzyme inhibitors (ACE-I) and angiotensin receptor blockers (ARBs) which are currently prescribed as safe antihypertensive therapies. Recent studies have explored the potential use of ACE-I and ARBs in breast cancer patients as anti-tumor agents. Therefore, it is vital to understand the role of RAS in breast cancer and identify mechanisms of Ang II and RAS inhibitors in the TME and in obesity and breast cancer crosstalk. In this review, we performed a detailed analysis and discussed mechanisms of Ang II-AT1R interactions in breast cancer with emphasis on obesity-associated breast cancer. We further summarized recent in vitro, in vivo and human studies that used ACE-I/ARB interventions to improve breast cancer outcomes.