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Role of the Renin–Angiotensin System Components in Renal Cell Carcinoma: A Literature Review

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Abstract

Purpose of Review

The physiological aspects of renin–angiotensin system (RAS) components are described in this review. Additionally, we present the main results of studies that could indicate an association between alterations in these components and cancer, particularly renal cell carcinoma (RCC).

Recent Findings

The RAS undergoes a series of homeostatic and modulatory processes that extend to hypertrophy, hyperplasia, fibrosis, and remodeling, as well as angiogenesis, pro-inflammatory responses, cell differentiation, stem cell programming, and hematopoiesis.

Summary

The link between cancer-related inflammation and RAS signaling converge in the response to tumor hypoxia and oxidative stress mechanisms, particularly with the angiotensin type 1 receptor leading to activation of transcription factors such as nuclear factor κB (NF-κB), as well as members of the signal transducer and activation of transcription (STAT) family and HIF1⍺. Dysregulation of the physiological actions of RAS in the microenvironment of inflammation and angiogenesis promotes tumor cell growth.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. • Capitanio U, Bensalah K, Bex A, Boorjian SA, Bray F, Coleman J, et al. Epidemiology of renal cell carcinoma. Eur Urol [Internet]. 2019;75:74–84. Available from: https://doi.org/10.1016/j.eururo.2018.08.036. A comprehensive and updated review of the epidemiology, including risk factors, of the renal cell carcinoma.

  2. Campbell SC, Lane BR, Pierorazio PM. Malignant renal tumors. In: Partin A, Dmochowski RR, Kavoussi L, Peters C, editors. Campbell-Walsh-Wein Urology. 12th ed. Filadélfia: Elsevier; 2021. p. 2133–84.

    Google Scholar 

  3. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin [Internet]. 2021;71:209–49. Available from: https://onlinelibrary.wiley.com/doi/10.3322/caac.21660.

  4. Snyder ME, Bach A, Kattan MW, Raj G V., Reuter VE, Russo P. Incidence of benign lesions for clinically localized renal masses smaller than 7 cm in radiological diameter: influence of sex. J Urol [Internet]. 2006;176:2391–6. Available from: http://www.jurology.com/doi/10.1016/j.juro.2006.08.013.

  5. Howlader N, Noone A-M, Krapcho M, Miller D, Brest A, Yu M, et al. SEER Cancer Statistics Review, 1975–2018, National Cancer Institute [Internet]. Bethesda, MD; 2021. Available from: https://seer.cancer.gov/csr/1975_2018/.

  6. Bandini M, Marchioni M, Pompe RS, Tian Z, Martel T, Chun FK, et al. The effect of age on cancer-specific mortality in patients with small renal masses: a population-based analysis. C Urol Assoc J [Internet]. 2018;12:E325–30. Available from: https://cuaj.ca/index.php/journal/article/view/4854.

  7. Macleod LC, Hotaling JM, Wright JL, Davenport MT, Gore JL, Harper J, et al. Risk factors for renal cell carcinoma in the VITAL study. J Urol [Internet]. 2013;190:1657–61. Available from: http://www.jurology.com/doi/10.1016/j.juro.2013.04.130.

  8. Hidayat K, Du X, Zou S-Y, Shi B-M. Blood pressure and kidney cancer risk. J Hypertens [Internet]. 2017;35:1333–44. Available from: https://journals.lww.com/00004872-201707000-00002.

  9. •• Ferreira DB, da Costa WH, Clavijo DA, Decia R, Cunha IW, Schultz L, et al. Tissue expression of erythropoietin predicts survival rates in clear cell renal cell carcinoma. Kidney Cancer [Internet]. 2017;1:143–9. Available from: https://www.medra.org/servlet/aliasResolver?alias=iospress&doi=10.3233/KCA-170013. A recent study analyzing the immunohistochemical expression of erythropoietin in samples of renal cell carcinoma.

  10. •• de Almeida e Paula F, Bezerra SM, da Cunha IW, Munhoz GC, Abreu D, Lara PN, et al. Immunohistochemical expression of renin is a prognostic factor for recurrence in nonmetastatic renal cell carcinoma. Urol Oncol [Internet]. 2019;37:947–54. Available from: https://linkinghub.elsevier.com/retrieve/pii/S1078143919302881. A study analyzing the immunohistochemical expression of renin in non-metastatic renal cell carcinoma.

  11. George AJ, Thomas WG, Hannan RD. The renin–angiotensin system and cancer: old dog, new tricks. Nat Rev Cancer [Internet]. Nature Publishing Group; 2010;10:745–59. Available from: https://doi.org/10.1038/nrc2945.

  12. Yin G, Yan C, Berk BC. Angiotensin II signaling pathways mediated by tyrosine kinases. Int J Biochem Cell Biol [Internet]. 2003;35:780–3. Available from: https://linkinghub.elsevier.com/retrieve/pii/S135727250200300X.

  13. Oro C, Qian H, Thomas WG. Type 1 angiotensin receptor pharmacology: signaling beyond G proteins. Pharmacol Ther [Internet]. 2007;113:210–26. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0163725806001835.

  14. Kranzhöfer R, Browatzki M, Schmidt J, Kübler W. Angiotensin II activates the proinflammatory transcription factor nuclear factor-κB in human monocytes. Biochem Biophys Res Commun [Internet]. 1999;257:826–8. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0006291X99905430.

  15. Aplin M, Bonde MM, Hansen JL. Molecular determinants of angiotensin II type 1 receptor functional selectivity. J Mol Cell Cardiol [Internet]. 2009;46:15–24. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0022282808007098.

  16. Hoch NE, Guzik TJ, Chen W, Deans T, Maalouf SA, Gratze P, et al. Regulation of T-cell function by endogenously produced angiotensin II. Am J Physiol Regul Integr Comp Physiol [Internet]. 2009;296:R208–16. Available from: https://www.physiology.org/doi/10.1152/ajpregu.90521.2008.

  17. Hackenthal E, Hackenthal R, Hilgenfeldt U. Isorenin, pseudorenin, cathepsin D and renin. A comparative enzymatic study of angiotensin-forming enzymes. Biochim Biophys Acta Enzymol [Internet]. 1978;522:574–88. Available from: https://linkinghub.elsevier.com/retrieve/pii/000527447890089X.

  18. Li Z, Wystrach L, Bernstein A, Grad S, Alini M, Richards R, et al. The tissue-renin-angiotensin-system of the human intervertebral disc. Eur Cell Mater [Internet]. 2020;40:115–32. Available from: https://www.ecmjournal.org/papers/vol040/pdf/v040a07.pdf.

  19. Sequeira López MLS, Pentz ES, Nomasa T, Smithies O, Gomez RA. Renin cells are precursors for multiple cell types that switch to the renin phenotype when homeostasis is threatened. Dev Cell [Internet]. 2004;6:719–28. Available from: https://linkinghub.elsevier.com/retrieve/pii/S1534580704001340.

  20. Sauter A, Machura K, Neubauer B, Kurtz A, Wagner C. Development of renin expression in the mouse kidney. Kidney Int [Internet]. 2008;73:43–51. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0085253815528184.

  21. Roth IM, Wickremesekera AC, Wickremesekera SK, Davis PF, Tan ST. Therapeutic targeting of cancer stem cells via modulation of the renin-angiotensin system. Front Oncol [Internet]. 2019;9:1–12. Available from: https://www.frontiersin.org/article/10.3389/fonc.2019.00745/full.

  22. Lindop GBM, Fleming S. Renin in renal cell carcinoma--an immunocytochemical study using an antibody to pure human renin. J Clin Pathol [Internet]. 1984;37:27–31. Available from: http://jcp.bmj.com/cgi/doi/10.1136/jcp.37.1.27.

  23. Arias LF, Bruneval P, Blanco J. Renin expression in adult renal epithelial tumors with granular cells. Pathol Res Pract [Internet]. Elsevier GmbH.; 2010;206:731–4. Available from: https://doi.org/10.1016/j.prp.2010.06.002.

  24. Chen S, Dong H, Yang S, Guo H. Cathepsins in digestive cancers. Oncotarget [Internet]. 2017;8:41690–700. Available from: https://www.oncotarget.com/lookup/doi/10.18632/oncotarget.16677.

  25. Morris BJ, Reid IA. A “Renin-Like” Enzymatic action of cathepsin D and the similarity in subcellular distributions of “renin-like” activity and cathepsin D in the midbrain of dogs*. Endocrinology [Internet]. 1978;103:1289–96. Available from: https://academic.oup.com/endo/article-lookup/doi/10.1210/endo-103-4-1289.

  26. Genest J, Cantin M, Garcia R, Thibault G, Gutkowska J, Schiffrin E, et al. Extrarenal angiotensin-forming enzymes. Clin Exp Hypertens A [Internet]. 1983;5:1065–80. Available from: http://www.tandfonline.com/doi/full/10.3109/10641968309048842.

  27. Walenbergh SMA, Houben T, Hendrikx T, Jeurissen MLJ, van Gorp PJ, Vreugdenhil ACE, et al. Plasma cathepsin D levels: a novel tool to predict pediatric hepatic inflammation. Am J Gastroenterol [Internet]. 2015;110:462–70. Available from: https://journals.lww.com/00000434-201503000-00020.

  28. Spyratos F, Hacene K, Rouëssé J, Brunet M, Andrieu C, Desplaces A, et al. Cathepsin D: an independent prognostic factor for metastasis of breast cancer. Lancet [Internet]. 1989;334:1115–8. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0140673689914876.

  29. Rochefort H, Capony F, Garcia M. Cathepsin D: A protease involved in breast cancer metastasis. Cancer Metastasis Rev [Internet]. 1990;9:321–31. Available from: http://link.springer.com/10.1007/BF00049522.

  30. Tandon AK, Clark GM, Chamness GC, Chirgwin JM, McGuire WL. Cathepsin D and prognosis in breast cancer. N Engl J Med [Internet]. 1990;322:297–302. Available from: http://www.nejm.org/doi/abs/10.1056/NEJM199002013220504.

  31. Wang F, Duan R, Chirgwin J, Safe S. Transcriptional activation of cathepsin D gene expression by growth factors. J Mol Endocrinol [Internet]. 2000;24:193–202. Available from: https://jme.bioscientifica.com/view/journals/jme/24/2/193.xml.

  32. Tumminello FM, Gebbia N, Pizzolanti G, Russo A, Bazan V, Leto G. Cathepsin D content in colorectal cancer. Oncology [Internet]. 1995;52:237–42. Available from: https://www.karger.com/Article/FullText/227464.

  33. Brouillet JP, Hanslick B, Maudelonde T, Pivat MT, Grenier J, Blanc F, et al. Increased plasma cathepsin D concentration in hepatic carcinoma and cirrhosis but not in breast cancer. Clin Biochem [Internet]. 1991;24:491–6. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0009912005800086.

  34. Podhajcer OL, Bover L, Bravo AI, Fernanda Ledda M, Kairiyama C, Calb I, et al. Expression of cathepsin D in primary and metastatic human melanoma and dysplastic nevi. J Investig Dermatol [Internet]. 1995;104:340–4. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0022202X15420615.

  35. Ross JS, Nazeer T, Figge HL, Fisher HAG, Rifkin MD. Quantitative immunohistochemical determination of cathepsin D levels in prostatic carcinoma biopsies: correlation with tumor grade, stage, PSA level, and DNA ploidy status. Am J Clin Pathol [Internet]. 1995;104:36–41. Available from: https://academic.oup.com/ajcp/article-lookup/doi/10.1093/ajcp/104.1.36.

  36. Benes P, Vetvicka V, Fusek M. Cathepsin D—Many functions of one aspartic protease. Crit Rev Oncol Hematol [Internet]. 2008;68:12–28. Available from: https://linkinghub.elsevier.com/retrieve/pii/S1040842808000486.

  37. Deiss LP, Galinka H, Berissi H, Cohen O, Kimchi A. Cathepsin D protease mediates programmed cell death induced by interferon-gamma, Fas/APO-1 and TNF-alpha. EMBO J [Internet]. 1996;15:3861–70. Available from: https://onlinelibrary.wiley.com/doi/10.1002/j.1460-2075.1996.tb00760.x.

  38. Ebert MPA, Krüger S, Fogeron M-L, Lamer S, Chen J, Pross M, et al. Overexpression of cathepsin B in gastric cancer identified by proteome analysis. Proteomics [Internet]. 2005;5:1693–704. Available from: https://onlinelibrary.wiley.com/doi/10.1002/pmic.200401030.

  39. Featherston T, Marsh RW, van Schaijik B, Brasch HD, Tan ST, Itinteang T. Expression and localization of cathepsins B, D, and G in two cancer stem cell subpopulations in moderately differentiated oral tongue squamous cell carcinoma. Front Med (Lausanne) [Internet]. 2017;4. Available from: http://journal.frontiersin.org/article/10.3389/fmed.2017.00100/full.

  40. Koh SP, Wickremesekera AC, Brasch HD, Marsh R, Tan ST, Itinteang T. Expression of cathepsins B, D, and G in isocitrate dehydrogenase-wild type glioblastoma. Front Surg [Internet]. 2017;4:1–9. Available from: http://journal.frontiersin.org/article/10.3389/fsurg.2017.00028/full.

  41. Mehrotra S, Wickremesekera SK, Brasch HD, Van Schaijik B, Marsh RW, Tan ST, et al. Expression and localization of cathepsins B, D and G in cancer stem cells in liver metastasis from colon adenocarcinoma. Front Surg [Internet]. 2018;5:1–9. Available from: https://www.frontiersin.org/article/10.3389/fsurg.2018.00040/full.

  42. Chen Z-Y, Wang Q-N, Zhu Y-H, Zhou L-Y, Xu T, He Z-Y, et al. Progress in the treatment of infantile hemangioma. Ann Transl Med [Internet]. 2019;7:692–692. Available from: http://atm.amegroups.com/article/view/30918/26804.

  43. Rahman RMA, van Schaijik B, Brasch HD, Marsh RW, Wickremesekera AC, Johnson R, et al. Expression of cathepsins B, D, and G in WHO grade I meningioma. Front Surg [Internet]. 2019;6:1–9. Available from: https://www.frontiersin.org/article/10.3389/fsurg.2019.00006/full.

  44. Merseburger AS, Hennenlotter J, Simon P, Ohneseit PA, Kuehs U, Kruck S, et al. Cathepsin D expression in renal cell cancer–clinical implications. Eur Urol [Internet]. 2005;48:519–26. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0302283805001533.

  45. Merseburger AS, Hennenlotter J, Stenzl A, Beger G, Rinnab L, Kuczyk MA, et al. Cathepsin D serum levels are not a valid serum marker in renal cell carcinoma. Urol Int [Internet]. 2007;79:41–3. Available from: https://www.karger.com/Article/FullText/102912.

  46. Vasudev NS, Sim S, Cairns DA, Ferguson RE, Craven RA, Stanley A, et al. Pre-operative urinary cathepsin D is associated with survival in patients with renal cell carcinoma. Br J Cancer [Internet]. Nature Publishing Group; 2009;101:1175–82. Available from: http://www.nature.com/articles/6605250.

  47. Eckardt K-U. Erythropoietin production in liver and kidneys. Curr Opin Nephrol Hypertens [Internet]. 1996;5:28–34. Available from: http://journals.lww.com/00041552-199601000-00007.

  48. Farrell F, Lee A. The erythropoietin receptor and its expression in tumor cells and other tissues. Oncologist [Internet]. 2004;9:18–30. Available from: https://academic.oup.com/oncolo/article/9/S5/18/6388134.

  49. Miyake M, Goodison S, Lawton A, Zhang G, Gomes-Giacoia E, Rosser CJ. Erythropoietin is a JAK2 and ERK1/2 effector that can promote renal tumor cell proliferation under hypoxic conditions. J Hematol Oncol [Internet]. 2013;6:65. Available from: https://jhoonline.biomedcentral.com/articles/10.1186/1756-8722-6-65.

  50. Morais C, Johnson DW, Vesey DA, Gobe GC. Functional significance of erythropoietin in renal cell carcinoma. BMC Cancer [Internet]. BMC Cancer; 2013;13:14. Available from: https://bmccancer.biomedcentral.com/articles/10.1186/1471-2407-13-14.

  51. Michael A, Politi E, Havranek E, Corbishley C, Karapanagiotou L, Anderson C, et al. Prognostic significance of erythropoietin expression in human renal cell carcinoma. BJU Int [Internet]. 2007;100:291–4. Available from: http://doi.wiley.com/10.1111/j.1464-410X.2007.06978.x.

  52. Nseyo UO, Williams PD, Murphy GE. Clinical significance of erythropoietin levels in renal carcinoma. Urology [Internet]. 1986;28:301–6. Available from: https://linkinghub.elsevier.com/retrieve/pii/0090429586900117.

  53. Westenfelder C, Baranowski RL. Erythropoietin stimulates proliferation of human renal carcinoma cells. Kidney Int [Internet]. 2000;58:647–57. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0085253815471455.

  54. Ito K, Yoshii H, Asano T, Horiguchi A, Sumitomo M, Hayakawa M, et al. Impact of increased erythropoietin receptor expression and elevated serum erythropoietin levels on clinicopathological features and prognosis in renal cell carcinoma. Exp Ther Med [Internet]. 2012;3:937–44. Available from: https://www.spandidos-publications.com/10.3892/etm.2012.513.

  55. Ljungberg B, Rasmuson T, Grankvist K. Erythropoietin in renal cell carcinoma: evaluation of its usefulness as a tumor marker. Eur Urol [Internet]. 1992;21:160–3. Available from: https://www.karger.com/Article/FullText/474825.

  56. Alamdari FI, Rasmuson T, Grankvist K, Ljungberg B. Angiogenesis and other markers for prediction of survival in metastatic renal cell carcinoma. Scand J Urol Nephrol [Internet]. 2007;41:5–9. Available from: https://www.tandfonline.com/doi/full/10.1080/00365590600830433.

  57. Mjønes PG, Nordrum IS, Qvigstad G, Sørdal Ø, Rian LLM, Waldum HL. Expression of erythropoietin and neuroendocrine markers in clear cell renal cell carcinoma. APMIS [Internet]. 2017;125:213–22. Available from: http://doi.wiley.com/10.1111/apm.12654.

  58. Gong K, Zhang N, Zhang Z, Na Y. Coexpression of erythropoietin and erythropoietin receptor in sporadic clear cell renal cell carcinoma. Cancer Biol Ther [Internet]. 2006;5:582–5. Available from: http://www.tandfonline.com/doi/abs/10.4161/cbt.5.6.2709.

  59. Papworth K, Bergh A, Grankvist K, Ljungberg B, Rasmuson T. Expression of Erythropoietin and Its Receptor in Human Renal Cell Carcinoma. Tumor Biol [Internet]. 2009;30:86–92. Available from: http://www.karger.com/doi/10.1159/000216844.

  60. Stoyanoff TR, Rodríguez JP, Todaro JS, Espada JD, Colavita JPM, Brandan NC, et al. Tumor biology of non-metastatic stages of clear cell renal cell carcinoma; overexpression of stearoyl desaturase-1, EPO/EPO-R system and hypoxia-related proteins. Tumor Biol [Internet]. 2016;37:13581–93. Available from: https://doi.org/10.1007/s13277-016-5279-4.

  61. •• Kurt B, Paliege A, Willam C, Schwarzensteiner I, Schucht K, Neymeyer H, et al. Deletion of von Hippel–Lindau protein converts renin-producing cells into erythropoietin-producing cells. J Am Soc Nephrol [Internet]. 2013;24:433–44. Available from: https://jasn.asnjournals.org/lookup/doi/10.1681/ASN.2012080791. An evidence of the interrelationship between renin and erythropoietin in kidney.

  62. Lever AF, Hole DJ, Gillis CR, McCallum IR, McInnes GT, MacKinnon PL, et al. Do inhibitors of angiotensin-I-converting enzyme protect against risk of cancer? Lancet [Internet]. 1998;352:179–84. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0140673698032280.

  63. Araújo WF, Naves MA, Ravanini JN, Schor N, Teixeira VPC. Renin-angiotensin system (RAS) blockade attenuates growth and metastatic potential of renal cell carcinoma in mice. Urologic Oncology: Seminars and Original Investigations [Internet]. Elsevier; 2015;33:389.e1–389.e7. Available from: https://doi.org/10.1016/j.urolonc.2014.11.022.

  64. McKay RR, Rodriguez GE, Lin X, Kaymakcalan MD, Hamnvik OPR, Sabbisetti VS, et al. Angiotensin system inhibitors and survival outcomes in patients with metastatic renal Cell Carcinoma. Clin Cancer Res. 2015;21:2471–9. Available from: https://doi.org/10.1158/1078-0432.CCR-14-2332.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Miyajima A, Yazawa S, Kosaka T, Tanaka N, Shirotake S, Mizuno R, et al. Prognostic impact of renin–angiotensin system blockade on renal cell carcinoma after surgery. Ann Surg Oncol [Internet]. 2015;22:3751–9. Available from: http://link.springer.com/10.1245/s10434-015-4436-0.

  66. Derosa L, Izzedine H, Albiges L, Escudier B. Hypertension and angiotensin system inhibitors in patients with metastatic renal cell carcinoma. Oncol Rev [Internet]. 2016;10:54–9. Available from: https://www.oncologyreviews.org/site/article/view/298.

  67. Rigat B, Hubert C, Alhenc-Gelas F, Cambien F, Corvol P, Soubrier F. An insertion/deletion polymorphism in the angiotensin I-converting enzyme gene accounting for half the variance of serum enzyme levels. J Clin Investig [Internet]. 1990;86:1343–6. Available from: http://www.jci.org/articles/view/114844.

  68. Medeiros R, Vasconcelos A, Costa S, Pinto D, Lobo F, Morais A, et al. Linkage of angiotensin I-converting enzyme gene insertion/deletion polymorphism to the progression of human prostate cancer. J Pathol [Internet]. 2004;202:330–5. Available from: https://onlinelibrary.wiley.com/doi/10.1002/path.1529.

  69. Ebert MPA. The angiotensin I-converting enzyme gene insertion/deletion polymorphism is linked to early gastric cancer. Cancer Epidemiol Biomarkers Prev [Internet]. 2005;14:2987–9. Available from: http://cebp.aacrjournals.org/cgi/doi/10.1158/1055-9965.EPI-05-0411.

  70. van der Knaap R, Siemes C, Coebergh J-WW, van Duijn CM, Hofman A, Stricker BHCh. Renin-angiotensin system inhibitors, angiotensin I-converting enzyme gene insertion/deletion polymorphism, and cancer. Cancer [Internet]. 2008;112:748–57. Available from: https://onlinelibrary.wiley.com/doi/10.1002/cncr.23215.

  71. Rhodes DR, Ateeq B, Cao Q, Tomlins SA, Mehra R, Laxman B, et al. AGTR1 overexpression defines a subset of breast cancer and confers sensitivity to losartan, an AGTR1 antagonist. Proc Natl Acad Sci [Internet]. 2009;106:10284–9. Available from: http://www.pnas.org/cgi/doi/10.1073/pnas.0900351106.

  72. Marrero MB, Schieffer B, Paxton WG, Heerdt L, Berk BC, Delafontaine P, et al. Direct stimulation of Jak/STAT pathway by the angiotensin II AT1 receptor. Nature [Internet]. 1995;375:247–50. Available from: http://www.nature.com/articles/375247a0.

  73. Pagé EL, Robitaille GA, Pouysségur J, Richard DE. Induction of Hypoxia-inducible Factor-1α by Transcriptional and Translational Mechanisms. J Biol Chem [Internet]. 2002;277:48403–9. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0021925819330728.

  74. Smith GR, Missailidis S. Cancer, inflammation and the AT1 and AT2 receptors. J Inflamm (Lond) [Internet]. 2004;1:3. Available from: http://www.ncbi.nlm.nih.gov/pubmed/15813980.

  75. Deshayes F, Nahmias C. Angiotensin receptors: a new role in cancer? Trends Endocrinol Metab [Internet]. 2005;16:293–9. Available from: https://linkinghub.elsevier.com/retrieve/pii/S1043276005001566.

  76. Hunyady L, Catt KJ. Pleiotropic AT1 receptor signaling pathways mediating physiological and pathogenic actions of angiotensin II. Mol Endocrinol [Internet]. 2006;20:953–70. Available from: https://academic.oup.com/mend/article/20/5/953/2738111.

  77. Ager EI, Neo J, Christophi C. The renin-angiotensin system and malignancy. Carcinogenesis [Internet]. 2008;29:1675–84. Available from: https://academic.oup.com/carcin/article-lookup/doi/10.1093/carcin/bgn171.

  78. Clere N, Corre I, Faure S, Guihot A-L, Vessières E, Chalopin M, et al. Deficiency or blockade of angiotensin II type 2 receptor delays tumorigenesis by inhibiting malignant cell proliferation and angiogenesis. Int J Cancer [Internet]. 2010;127:2279–91. Available from: https://onlinelibrary.wiley.com/doi/10.1002/ijc.25234.

  79. Dolley-Hitze T, Jouan F, Martin B, Mottier S, Edeline J, Moranne O, et al. Angiotensin-2 receptors (AT1-R and AT2-R), new prognostic factors for renal clear-cell carcinoma? Br J Cancer [Internet]. Nature Publishing Group; 2010;103:1698–705. Available from: https://doi.org/10.1038/sj.bjc.6605866.

  80. Errarte P, Beitia M, Perez I, Manterola L, Lawrie CH, Solano-Iturri JD, et al. Expression and activity of angiotensin-regulating enzymes is associated with prognostic outcome in clear cell renal cell carcinoma patients. Bottaro DP, editor. PLoS One [Internet]. 2017;12:e0181711. Available from: https://dx.plos.org/10.1371/journal.pone.0181711.

  81. Harris AL. Hypoxia — a key regulatory factor in tumour growth. Nat Rev Cancer [Internet]. 2002;2:38–47. Available from: http://www.nature.com/articles/nrc704.

  82. Lane BR, Rini BI, Novick AC, Campbell SC. Targeted molecular therapy for renal cell carcinoma. Urology [Internet]. 2007;69:3–10. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0090429506021522.

  83. Maxwell PH, Wiesener MS, Chang G-W, Clifford SC, Vaux EC, Cockman ME, et al. The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis. Nature [Internet]. 1999;399:271–5. Available from: https://www.nature.com/articles/20459.

  84. Young AC, Craven RA, Cohen D, Taylor C, Booth C, Harnden P, et al. Analysis of VHL gene alterations and their relationship to clinical parameters in sporadic conventional renal cell carcinoma. Clin Cancer Res [Internet]. 2009;15:7582–92. Available from: http://clincancerres.aacrjournals.org/cgi/doi/10.1158/1078-0432.CCR-09-2131.

  85. Bratslavsky G, Sudarshan S, Neckers L, Linehan WM. Pseudohypoxic pathways in renal cell carcinoma. Clin Cancer Res [Internet]. 2007;13:4667–71. Available from: http://clincancerres.aacrjournals.org/lookup/doi/10.1158/1078-0432.CCR-06-2510.

  86. Caro JJ, Salas M, Ward A, Goss G. Anemia as an independent prognostic factor for survival in patients with cancer: a systemic, quantitative review. Cancer [Internet]. 2001;91:2214–21. Available from: http://www.ncbi.nlm.nih.gov/pubmed/11413508.

  87. Vaupel P. Oxygenation status of malignant tumors: Pathogenesis of hypoxia and significance for tumor therapy. Semin Oncol [Internet]. 2001;28:29–35. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0093775401902106.

  88. Zequi SDC, Mourão TC, de Oliveira MM, Curado MP, Gueglio G, da Costa WH, et al. Predictors of survival outcomes in non-metastatic renal cell carcinoma in Latin America and Spain: a multicentric analysis. Kidney Cancer. 2019;3:253–61. Available from: https://content.iospress.com/articles/kidney-cancer/kca190068.

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  1. Department of Urology, Fundação Antônio Prudente, A.C. Camargo Cancer Center, São Paulo, Brazil

    Thiago Camelo Mourão, Victor Espinheira Santos, Eder Silveira Brazão Jr, Walter Henriques da Costa & Stênio de Cássio Zequi

  2. Department of Pathological Anatomy, Fundação Antônio Prudente, A.C. Camargo Cancer Center, Rua Prof. Antônio Prudente, São Paulo, 211, Brazil

    Stephania Martins Bezerra

  3. National Institute for Science and Technology in Oncogenomics and Therapeutic Innovation, São Paulo, Brazil

    Walter Henriques da Costa & Stênio de Cássio Zequi

  4. Graduate School, Department of Surgery, Division of Urology, São Paulo Federal University, São Paulo, Brazil

    Stênio de Cássio Zequi

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  1. Thiago Camelo Mourão
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  3. Victor Espinheira Santos
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  6. Stênio de Cássio Zequi
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Correspondence to Thiago Camelo Mourão.

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Mourão, T.C., Bezerra, S.M., Santos, V.E. et al. Role of the Renin–Angiotensin System Components in Renal Cell Carcinoma: A Literature Review. Curr Urol Rep 24, 345–353 (2023). https://doi.org/10.1007/s11934-023-01160-x

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