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Expression of angiotensin II type 2 receptors and syndecan-1 in prostate cancer

https://doi.org/10.21886/2308-6424-2024-12-5-45-54

Abstract

Introduction. Prostate cancer (PCa) remains an urgent problem of modern oncological urology due to high morbidity and mortality rates.

Objective. To evaluate the expression of angiotensin II type 2 receptor (AT2-R) and syndecan-1 (CD138) receptors in prostatic intraepithelial neoplasia (PIN) and PCa.

Materials & methods. For the immunohistochemical (IHC) study, the prostate biopsy cores of 20 men was used: 10 men with PIN, 10 men with PCa. Primary antibodies to AT2-R and CD138 antibodies were used for IHC staining, the EnVision FLEX imaging system. Formulation of IHC reactions, interpretation of the results obtained were carried out according to generally accepted rules.

Results. The results of the study showed that AT2-R deficiency increases in the range of PIN-3 – PCa. Mild AT2-R expression or its absence was noted in tumor cells with PCa, while the AT2-R localisation was nuclear. In PIN-3, the expression of syndecan-1 was localised on the membrane of basal cells and the basolateral side of secretory epithelial cells, without expression in the adjacent stroma, while the expression level of syndecan-1 always remained high. In PCa, the membrane expression of syndecan-1 was preserved. With a decrease or absence of AT2-R nuclear expression in PCa tissue with an increase in ISUP, the expression level of syndecan-1 decreased.

Conclusion. Simultaneous decrease in the expression levels of AT2-R and syndecan-1 in PCa has been demonstrated for the first time. A comprehensive determination of the expression levels of AT2-R and syndecan-1 seems to be promising for the development of diagnostic and prognostic markers of PCa initiation and development.

About the Authors

E. A. Chernogubova
Federal Research Centre the Southern Scientific Centre of the Russian Academy of Sciences
Russian Federation

Elena A. Chernogubova —Cand.Sc.(Biol).

Rostov-on-Don


Competing Interests:

None



A. V. Avetyan
Rostov State Medical University
Russian Federation

Andrey V. Avetyan.

Rostov-on-Don


Competing Interests:

None



M. B. Chibichyan
Rostov State Medical University
Russian Federation

Mikael B. Chibichyan —Dr.Sc.(Med), Assoc.Prof.(Docent).

Rostov-on-Don


Competing Interests:

None



M. I. Kogan
Federal Research Centre the Southern Scientific Centre of the Russian Academy of Sciences; Rostov State Medical University
Russian Federation

Mikhail I. Kogan — Dr.Sc.(Med), Full Prof., Hons. Sci. of the Russian Federation.

Rostov-on-Don


Competing Interests:

None



References

1. Kaprin A.D., Starinsky V.V., Shakhzadova A.O. Malignant tumors in Russia in 2021 (morbidity and mortality). Moscow: P.A. Gertsen Moscow Research Oncological Institute, Branch of the Federal State Budgetary Institution “National Medical Research Radiological Center” of the Ministry of Health of Russia; 2024. (In Russian).

2. Siegel RL, Giaquinto AN, Jemal A. Cancer statistics, 2024. CA Cancer J Clin. 2024;74(1):12-49. Erratum in: CA Cancer J Clin. 2024;74(2):203. DOI: 10.3322/caac.21820

3. Krasnyak S.S. Pathogenetic therapy of benign prostatic hyperplasia and prostatic intraepithelial neoplasia. Experimental and Clinical Urology. 2020(4):66-74. (In Russian). DOI: 10.29188/2222-8543-2020-13-4-66-74

4. Kogan M.I., Akhokhov Z.M., Chernogubova E.A., Gusev A.A., Oitova Z.Kh. The role of the renin-angiotensin system in the appearance and progression of renal cell carcinoma: a literature review. Cancer Urology. 2019;15(3):143-149. (In Russian). DOI: 10.17650/1726-9776-2019-15-3-143-149

5. Chibichyan M.B., Chernogubova E.A., Avetyan A.V., Lapteva T.O., Pavlenko I.A., Kogan M.I. The role of angiotensin-converting enzyme and angiotensin ii receptors of the second type in the pathogenesis of proliferative diseases of the prostate. Urologiia. 2022;(1):5-10. (In Russian). DOI: 10.18565/urology.2022.1.5-10

6. Domińska K, Lachowicz-Ochedalska A. Zaangazowanie układu renina-angiotensyna (RAS) w proces kancerogenezy [The involvement of the renin-angiotensin system (RAS) in cancerogenesis]. Postepy Biochem. 2008;54(3):294-300. (In Polish). PMID: 19112828

7. Wolgien MCGM, Correa SAA, Breuel PAF, Nazário ACP, Facina G. Renin Angiotensin System Components and Cancer:Reports of Association. J. Biosci. Med. 2016;(4):65–75. DOI: 10.4236/jbm.2016.45007

8. D’Ardes D, Boccatonda A, Rossi I, Guagnano MT, Santilli F, Cipollone F, Bucci M. COVID-19 and RAS: Unravelling an Unclear Relationship. Int J Mol Sci. 2020;21(8):3003. DOI: 10.3390/ijms21083003

9. Teng YH, Aquino RS, Park PW. Molecular functions of syndecan-1 in disease. Matrix Biol. 2012;31(1):3-16. DOI: 10.1016/j.matbio.2011.10.001

10. Lazniewska J, Li KL, Johnson IRD, Sorvina A, Logan JM, Martini C, Moore C, Ung BS, Karageorgos L, Hickey SM, Prabhakaran S, Heatlie JK, Brooks RD, Huzzell C, Warnock NI, Ward MP, Mohammed B, Tewari P, Martin C, O’Toole S, Edgerton LB, Bates M, Moretti P, Pitson SM, Selemidis S, Butler LM, O’Leary JJ, Brooks DA. Dynamic interplay between sortilin and syndecan-1 contributes to prostate cancer progression. Sci Rep. 2023;13(1):13489. DOI: 10.1038/s41598-023-40347-7

11. Zhang Y, McKown RL, Raab RW, Rapraeger AC, Laurie GW. Focus on molecules: syndecan-1. Exp Eye Res. 2011;93(4):329-330. DOI: 10.1016/j.exer.2010.06.008

12. Chaudhary PK, Kim S. An Insight into GPCR and G-Proteins as Cancer Drivers. Cells. 2021;10(12):3288. DOI: 10.3390/cells10123288

13. Ahmad Fauzi MF, Wan Ahmad WSHM, Jamaluddin MF, Lee JTH, Khor SY, Looi LM, Abas FS, Aldahoul N. Allred Scoring of ER-IHC Stained Whole-Slide Images for Hormone Receptor Status in Breast Carcinoma. Diagnostics (Basel). 2022;12(12):3093. DOI: 10.3390/diagnostics12123093

14. Rebrova O.Ju. Statistical analysis of medical data. Using the STATISTICA Application Package. Moscow: MediaSfera; 2002. (In Russian).

15. Kaschina E, Unger T. Angiotensin AT1/AT2 receptors: regulation, signalling and function. Blood Press. 2003;12(2):70-88. DOI: 10.1080/08037050310001057

16. Singh KD, Karnik SS. Angiotensin Receptors: Structure, Function, Signaling and Clinical Applications. J Cell Signal. 2016;1(2):111. DOI: 10.4172/jcs.1000111

17. Septiadi SS, Noegroho BS, Tjahjodjati T, Safriadiet F., Siregar S, Adriansjahal R, Adi K, Si-hombing AT, Pramod SV, Nasution R, Hernowo BS. Angiotensin II type-1 receptor (AT1R) distribution in BPH, high grade PIN and adenocarcinoma of the prostate. Indonesian Journal of Urology. 2010;17(2):55-57. DOI: 10.32421/juri.v17i2.348

18. Santos NJ, Barquilha CN, Barbosa IC, Macedo RT, Lima FO, Justulin LA, Barbosa GO, Carvalho HF, Felisbino SL. Syndecan Family Gene and Protein Expression and Their Prognostic Values for Prostate Cancer. Int J Mol Sci. 2021;22(16):8669. DOI: 10.3390/ijms22168669

19. Logan JM, Martini C, Sorvina A, Johnson IRD, Brooks RD, Caruso MC, Huzzell C, Moore CR, Karageorgos L, Butler LM, Tewari P, Prabhakaran S, Hickey SM, Klebe S, Samaratunga H, Delahunt B, Moretti K, O’Leary JJ, Brooks DA, Ung BS. Reinterpretation of prostate cancer pathology by Appl1, Sortilin and Syndecan-1 biomarkers. Sci Data. 2024;11(1):852. DOI: 10.1038/s41597-024-03696-0

20. Leonova E.I., Galzitskaya O.V. Comparative characteristics of the structure and function for animal syndecan-1 proteins. Molecular Biology. 2013;47(3): 505-512. (In Russian). DOI: 10.7868/S0026898413030075

21. Kind S, Kluth M, Hube-Magg C, Möller K, Makrypidi-Fraune G, Lutz F, Lennartz M, Rico SD, Schlomm T, Heinzer H, Höflmayer D, Weidemann S, Uhlig R, Huland H, Graefen M, Bernreuther C, Tsourlakis MC, Minner S, Dum D, Hinsch A, Lübke AM, Simon R, Sauter G, Marx A, Polonski A. Increased Cytoplasmic CD138 Expression Is Associated with Aggressive Characteristics in Prostate Cancer and Is an Independent Predictor for Biochemical Recurrence. Biomed Res Int. 2020;2020:5845374. DOI: 10.1155/2020/5845374

22. Szarvas T, Sevcenco S, Módos O, Keresztes D, Nyirády P, Kubik A, Romics M, Kovalszky I, Reis H, Hadaschik B, Shariat SF, Kramer G. Circulating syndecan-1 is associated with chemotherapy-resistance in castration-resistant prostate cancer. Urol Oncol. 2018;36(6):312.e9-312.e15. DOI: 10.1016/j.urolonc.2018.03.010

23. Shimada K, Anai S, Fujii T, Tanaka N, Fujimoto K, Konishi N. Syndecan-1 (CD138) contributes to prostate cancer progression by stabilizing tumour-initiating cells. J Pathol. 2013;231(4):495-504. DOI: 10.1002/path.4271

24. Kogan M.I., Chernogubova E.A., Chibichyan M.B., Matishov D.G. Angiotensin converting enzyme — a new prognostic marker of recurrence in the treatment of prostate cancer. Cancer Urology. 2016;12(4):87-93. (In Russian). DOI: 10.17650/1726-9776-2016-12-4-87-93

25. Chibichyan M.B., Kogan M.I., Chernogubova E.A. et al. Role of angiotensin II receptor type 2 in predicting biochemical recurrence in the treatment of prostate cancer. Urologiia. 2016;(6):89-94. (In Russian).

26. Csermely P, Korcsmáros T, Kiss HJ, London G, Nussinov R. Structure and dynamics of molecular networks: a novel paradigm of drug discovery: a comprehensive review. Pharmacol Ther. 2013;138(3):333-408. DOI: 10.1016/j.pharmthera.2013.01.016

27. Shpakov A.O. Angiotensin-Converting Enzyme of the Type 2 as a Molecular Mediator for the Entry of SARS-Cov and SARS-Cov-2 Viruses into the Cell. Russian Journal of Physiology. 106(6):795–810. (In Russian). DOI: 10.31857/S086981392006013

28. Sehn F, Büttner H, Godau B, Müller M, Sarcan S, Offermann A, Perner S, Kramer MW, Merseburger AS, Roesch MC. The alternative renin-angiotensin-system (RAS) signalling pathway in prostate cancer and its link to the current COVID-19 pandemic. Mol Biol Rep. 2023;50(2):1809-1816. DOI: 10.1007/s11033-022-08087-5

29. Gujrati H, Ha S, Wang BD. Deregulated microRNAs Involved in Prostate Cancer Aggressiveness and Treatment Resistance Mechanisms. Cancers (Basel). 2023;15(12):3140. DOI: 10.3390/cancers15123140

30. Imyanitov E.N. Epidemiology and biology of prostate cancer. Practical oncology. 2008;9(2):57-64. (In Russian). eLIBRARY ID: 19130354; EDN: QCQJKL

31. Zhou J, Du T, Li B, Rong Y, Verkhratsky A, Peng L. Crosstalk Between MAPK/ERK and PI3K/AKT Signal Pathways During Brain Ischemia/ Reperfusion. ASN Neuro. 2015;7(5):1759091415602463. DOI: 10.1177/1759091415602463

32. Butler DE, Marlein C, Walker HF, Frame FM, Mann VM, Simms MS, Davies BR, Collins AT, Maitland NJ. Inhibition of the PI3K/AKT/mTOR pathway activates autophagy and compensatory Ras/Raf/MEK/ERK signalling in prostate cancer. Oncotarget. 2017;8(34):56698-56713. DOI: 10.18632/oncotarget.18082

33. Shorning BY, Dass MS, Smalley MJ, Pearson HB. The PI3K-AKT-mTOR Pathway and Prostate Cancer: At the Crossroads of AR, MAPK, and WNT Signaling. Int J Mol Sci. 2020;21(12):4507. DOI: 10.3390/ijms21124507

34. Sadrkhanloo M, Paskeh MDA, Hashemi M, Raesi R, Motahhary M, Saghari S, Sharifi L, Bokaie S, Mirzaei S, Entezari M, Aref AR, Salimimoghadam S, Rashidi M, Taheriazam A, Hushmandi K. STAT3 signaling in prostate cancer progression and therapy resistance: An oncogenic pathway with diverse functions. Biomed Pharmacother. 2023;158:114168. DOI: 10.1016/j.biopha.2022.114168

35. Luo J, Zha S, Gage WR, Dunn TA, Hicks JL, Bennett CJ, Ewing CM, Platz EA, Ferdinandusse S, Wanders RJ, Trent JM, Isaacs WB, De Marzo AM. Alphamethylacyl-CoA racemase: a new molecular marker for prostate cancer. Cancer Res. 2002;62(8):2220-2226. PMID: 11956072


Review

For citations:


Chernogubova E.A., Avetyan A.V., Chibichyan M.B., Kogan M.I. Expression of angiotensin II type 2 receptors and syndecan-1 in prostate cancer. Urology Herald. 2024;12(5):45-54. (In Russ.) https://doi.org/10.21886/2308-6424-2024-12-5-45-54

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ISSN 2308-6424 (Online)