title: Hypoxia induces dysregulation of local renin-angiotensin system in mouse Lewis lung carcinoma cells.
abstract: The renin-angiotensin system (RAS) influences cancer biology and is frequently dysregulated in malignancy. However, regulation of tumor local RAS remains poorly understood. Hypoxia is a hallmark of solid tumors and affects nearly every major aspect of cancer biology. Previous studies have shown that hypoxia can regulate RAS expression in somatic tissues and cells. The aim of this study was to investigate the influence of hypoxia on local RAS expression in mouse Lewis lung carcinoma (LLC) cells. For hypoxia treatment, LLC cells were cultured in a hypoxia incubator or treated with hypoxia-mimetic cobalt chloride. Hypoxia up-regulated angiotensin II, angiotensin-converting enzyme (ACE), and angiotensin II type 1 receptor (AT1R), and down-regulated ACE2 and angiotensin II type 2 receptor in LLC cells. Captopril, an ACE inhibitor, and losartan, an AT1R blocker, decreased expression of ACE and AT1R, but increased expression of ACE2 and angiotensin II type 2 receptor in LLC cells under hypoxia. Captopril and losartan also suppressed vascular endothelial growth factor-A expression in LLC cells under hypoxia. These findings suggest that hypoxia induces dysregulation of local RAS in LLC cells. The pathophysiological importance of hypoxia-induced RAS dysregulation and potentially therapeutic effects of RAS inhibitors on hypoxic tumor cells should be further examined.
authors.affiliation: Department of Respiration, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: L
authors.initials: L
authors.lastname: Fan
authors.affiliation: Department of Respiration, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Department of Respiration, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China wanhuanyingruijin@gmail.com.
authors.forename: H Y
authors.initials: HY
authors.lastname: Wan
authors.affiliation: Department of Respiration, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: L
authors.initials: L
authors.lastname: Ni
authors.affiliation: Department of Respiration, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Y R
authors.initials: YR
authors.lastname: Qian
authors.affiliation: Department of Respiration, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Respiration, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Xiang
authors.affiliation: Department of Respiration, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Q Y
authors.initials: QY
authors.lastname: Li
mesh_terms: D000804:Angiotensin II / Q000096:biosynthesis; D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D018827:Carcinoma, Lewis Lung / Q000235:genetics* / Q000503:physiopathology / Q000628:therapy; D015687:Cell Hypoxia; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007703:Peptidyl-Dipeptidase A / Q000096:biosynthesis; D044139:Receptor, Angiotensin, Type 2 / Q000096:biosynthesis; D012084:Renin-Angiotensin System / Q000235:genetics*
chemical_list: D044139:Receptor, Angiotensin, Type 2; D000804:Angiotensin II; C488034:ACE protein, human; D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; C000705328:Ace2 protein, mouse; D000085962:Angiotensin-Converting Enzyme 2