Volume 11, Issue 3 (Vol.11 No.3 Oct 2022)                   rbmb.net 2022, 11(3): 411-420 | Back to browse issues page


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Zahiri E, Ghorbani H, Moradi A, Mehrad-Majd H, Mohammadi F, Sharifi Sistani N et al . Prognostic Significance of Substance P and Neurokinin-1 Receptor in Bladder Cancer. rbmb.net 2022; 11 (3) :411-420
URL: http://rbmb.net/article-1-912-en.html
Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran & Surgical Oncology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
Abstract:   (369 Views)
Background: Bladder cancer is one of the most common genitourinary cancers with significant mortality. Finding reliable tumor markers and potential drug targets can improve early diagnosis, prognosis, and more effective therapeutic protocols. Previous studies have reported the involvement of the substance P (SP)/neurokinin-1 receptor (NK-1R) system in cancers. The potential prognostic role and the interaction of SP and NK-1R in bladder tumor are yet to be elucidated.

Methods: Serum samples from 22 primarily diagnosed patients with bladder cancer as well as 22 healthy controls were examined for SP level using ELISA method. Tissue distribution of NK-1R in tumor samples and their adjacent normal tissues was evaluated through immunohistochemistry.
esults: Serum SP levels in patients with bladder cancer were higher than the healthy group (p< 0.001) and had a significant correlation with NK-1R staining intensity (p< 0.001), percentage of stained cells (p< 0.001), and NK-1R tissue distribution. Also, the immunoreactivity of NK-1R in cancer samples increased significantly without correlation with tumor characteristics. However, no significant association was found between SP and NK-1R levels with clinical characteristics including tumor size (p= 0.33), tumor stage (p= 0.29), grade (p= 0.93), NK-1R staining intensity (p= 0.53), and percentage of stained cells (p= 0.32).


Conclusions: According to our findings, despite the lack of association between SP and NK-1R with clinical characteristics of bladder cancer, their serum levels were higher in patients with bladder cancer. Further studies are needed to confirm the potential prognostic role of SP and NK-1R in bladder cancer.
Full-Text [PDF 292 kb]   (120 Downloads)    
Type of Article: Original Article | Subject: Biochemistry
Received: 2022/04/10 | Accepted: 2022/06/25 | Published: 2022/12/31

References
1. Brothers SP, Wahlestedt C. Therapeutic potential of neuropeptide Y (NPY) receptor ligands. EMBO Mol Med. 2010;2(11):429-39. [DOI:10.1002/emmm.201000100] [PMID] [PMCID]
2. Munoz M, Covenas R. Involvement of substance P and the NK-1 receptor in cancer progression. Peptides. 2013;48:1-9. [DOI:10.1016/j.peptides.2013.07.024] [PMID]
3. Hashemian P, Javid H, Tadayyon Tabrizi A, Hashemy SI. The Role of Tachykinins in the Initiation and Progression of Gastrointestinal Cancers: A Review. Int J Cancer Manag. 2020;13(5):e100717. [DOI:10.5812/ijcm.100717]
4. Covenas R, Munoz M. Cancer progression and substance P. Histol Histopathol. 2014;29(7):881-90.
5. Ebrahimi S, Javid H, Alaei A, Hashemy SI. New insight into the role of substance P/neurokinin-1 receptor system in breast cancer progression and its crosstalk with microRNAs. Clin Genet. 2020;98(4):322-330. [DOI:10.1111/cge.13750] [PMID]
6. Morgat C, Mishra AK, Varshney R, Allard M, Fernandez P, Hindié E. Targeting neuropeptide receptors for cancer imaging and therapy: perspectives with bombesin, neurotensin, and neuropeptide-Y receptors. Journal of Nuclear Medicine. 2014;55(10):1650-1657. [DOI:10.2967/jnumed.114.142000] [PMID]
7. Munoz M, Rosso M, Covenas R. The NK-1 receptor: a new target in cancer therapy. Current drug targets. 2011;12(6):909-21. [DOI:10.2174/138945011795528796] [PMID]
8. Steinhoff MS, von Mentzer B, Geppetti P, Pothoulakis C, Bunnett NW. Tachykinins and their receptors: contributions to physiological control and the mechanisms of disease. Physiol Rev. 2014;94(1):265-301. [DOI:10.1152/physrev.00031.2013] [PMID] [PMCID]
9. Helke C, Krause J, Mantyh PW, Couture R, Bannon M. Diversity in mammalian tachykinin peptidergic neurons: multiple peptides, receptors, and regulatory mechanisms. The FASEB J. 1990;4(6):1606-15. [DOI:10.1096/fasebj.4.6.1969374] [PMID]
10. Euler U, Gaddum J. An unidentified depressor substance in certain tissue extracts. J Physiol. 1931;72(1):74-87. [DOI:10.1113/jphysiol.1931.sp002763] [PMID] [PMCID]
11. Liu L, Burcher E. Tachykinin peptides and receptors: putting amphibians into perspective. Peptides. 2005;26(8):1369-82. [DOI:10.1016/j.peptides.2005.03.027] [PMID]
12. Bossaller C, Reither K, Hehlert-Friedrich C, Auch-Schwelk W, Graf K, Gräfe M, et al. In vivo measurement of endothelium-dependent vasodilation with substance P in man. Herz. 1992;17(5):284-90.
13. De Felipe C, Herrero JF, O'Brien JA, Palmer JA, Doyle CA, Smith AJ, et al. Altered nociception, analgesia and aggression in mice lacking the receptor for substance P. Nature. 1998;392(6674):394-7. [DOI:10.1038/32904] [PMID]
14. Ebner K, Singewald N. The role of substance P in stress and anxiety responses. Amino acids. 2006;31(3):251-72. [DOI:10.1007/s00726-006-0335-9] [PMID]
15. Huston J, Hasenöhrl R, Boix F, Gerhardt P, Schwarting R. Sequence-specific effects of neurokinin substance P on memory, reinforcement, and brain dopamine activity. Psychopharmacology. 1993;112(2-3):147-62. [DOI:10.1007/BF02244906] [PMID]
16. Rameshwar P, Gascon P, Ganea D. Immunoregulatory effects of neuropeptides. Stimulation of interleukin-2 production by substance P. J Neuroimmunol. 1992;37(1-2):65-74. [DOI:10.1016/0165-5728(92)90156-F] [PMID]
17. Marchand JE, Sant GR, Kream RM. Increased expression of substance P receptor-encoding mRNA in bladder biopsies from patients with interstitial cystitis. Br J Urol. 1998;81(2):224-8. [DOI:10.1046/j.1464-410X.1998.00507.x] [PMID]
18. Fadaee J, Khoshkhui M, Emadzadeh M, Hashemy SI, Hosseini RF, Azad FJ, et al. Evaluation of Serum Substance P Level in Chronic Urticaria and Correlation with Disease Severity. Iranian J Allergy Asthma Immunol. 2020:19(1):18-26. [DOI:10.18502/ijaai.v19i1.2414] [PMID]
19. Khorasani S, Boroumand N, Lavi Arab F, Hashemy SI. The immunomodulatory effects of tachykinins and their receptors. Journal of Cellular Biochemistry. 2020;121(5-6):3031-3041. [DOI:10.1002/jcb.29668] [PMID]
20. Kaplan AL, Litwin MS, Chamie K. The future of bladder cancer care in the USA. Nature reviews Urology. 2014;11(1):59. [DOI:10.1038/nrurol.2013.180] [PMID]
21. Malats N, Real FX. Epidemiology of bladder cancer. Hematology/oncology clinics. 2015;29(2):177-89. [DOI:10.1016/j.hoc.2014.10.001] [PMID]
22. Candenas L, Lecci A, Pinto FM, Patak E, Maggi CA, Pennefather JN. Tachykinins and tachykinin receptors: effects in the genitourinary tract. Life sciences. 2005;76(8):835-862. [DOI:10.1016/j.lfs.2004.10.004] [PMID]
23. Lecci A, Maggi CA. Tachykinins as modulators of the micturition reflex in the central and peripheral nervous system. Regul Pept. 2001;101(1-3):1-18. [DOI:10.1016/S0167-0115(01)00285-3] [PMID]
24. Pennefather JN, Lecci A, Candenas ML, Patak E, Pinto FM, Maggi CA. Tachykinins and tachykinin receptors: a growing family. Life Sci. 2004;74(12):1445-63. [DOI:10.1016/j.lfs.2003.09.039] [PMID]
25. Quartara L, Maggi C. The tachykinin NK1 receptor. Part II: Distribution and pathophysiological roles. Neuropeptides. 1998;32(1):1-49. [DOI:10.1016/S0143-4179(98)90015-4] [PMID]
26. Hammond TG, Saban R, Bost KL, Harris HW, Jr Kaysen JH, Goda FO, et al. Substance P dependence of endosomal fusion during bladder inflammation. Am J Physiol Renal Physiol. 2000;278(3):F440-51. [DOI:10.1152/ajprenal.2000.278.3.F440] [PMID]
27. Bjorling DE, Beckman M, Saban R. Neurogenic inflammation of the bladder. Adv Exp Med Biol. 2003;539(Pt B):551-83. [DOI:10.1007/978-1-4419-8889-8_37] [PMID]
28. Busser BW, Hammond TG, Bjorling DE, Saban R. Lipopolysaccharide upregulates bradykinin 1 receptors in the isolated mouse bladder. J Urol. 1998;160(6 Pt 1):2267-73. [DOI:10.1016/S0022-5347(01)62308-5] [PMID]
29. Dozmorov I, Saban MR, Knowlton N, Centola M, Saban R. Connective molecular pathways of experimental bladder inflammation. Physiol Genomics. 2003;15(3):209-22. [DOI:10.1152/physiolgenomics.00130.2003] [PMID]
30. Jerde TJ, Saban R, Nakada SY. Evaluation of ureteric contraction: a comparison among ring, spiral-cut and longitudinal segments. BJU international. 1999;83(1):95-100. [DOI:10.1046/j.1464-410x.1999.00865.x] [PMID]
31. Jerde TJ, Saban R, Bjorling DE, Steinberg H, Nakada SY. Distribution of neuropeptides, histamine content, and inflammatory cells in the ureter. Urology. 2000;56(1):173-8. [DOI:10.1016/S0090-4295(00)00559-8] [PMID]
32. Nakada SY, Jerde TJ, Bjorling DE, Saban R. In vitro contractile effects of neurokinin receptor blockade in the human ureter. J Urol. 2001;166(4):1534-8. https://doi.org/10.1016/S0022-5347(05)65826-0 [DOI:10.1097/00005392-200110000-00087] [PMID]
33. Saban R, Keith IM, Nielsen KT, Christensen MM, Rhodes PR, Bruskewitz RC. In vitro effects of bladder mucosa and an enkephalinase inhibitor on tachykinin induced contractility of the dog bladder. J Urol. 1992;147(3):750-5. [DOI:10.1016/S0022-5347(17)37372-X] [PMID]
34. Vizzard MA. Alterations in neuropeptide expression in lumbosacral bladder pathways following chronic cystitis. J Chem Neuroanat. 2001;21(2):125-38. [DOI:10.1016/S0891-0618(00)00115-0] [PMID]
35. Javid H, Mohammadi F, Zahiri E, Hashemy SI. The emerging role of substance P/neurokinin-1 receptor signaling pathways in growth and development of tumor cells. J Physiol Biochem. 2019:75(4):415-421. [DOI:10.1007/s13105-019-00697-1] [PMID]
36. Mohammadi F, Javid H, Afshari AR, Mashkani B, Hashemy SI. Substance P accelerates the progression of human esophageal squamous cell carcinoma via MMP‑2, MMP‑9, VEGF‑A, and VEGFR1 overexpression. Mol Biol Rep. 2020;47(6):4263-4272. [DOI:10.1007/s11033-020-05532-1] [PMID]
37. Marriott I, Mason MJ, Elhofy A, Bost KL. Substance P activates NF-κB independent of elevations in intracellular calcium in murine macrophages and dendritic cells. J Neuroimmunol. 2000;102(2):163-71. [DOI:10.1016/S0165-5728(99)00182-4] [PMID]
38. Ni T, Liu Y, Peng Y, Li M, Fang Y, Yao M. Substance P induces inflammatory responses involving NF-κB in genetically diabetic mice skin fibroblasts co-cultured with macrophages. Am J Transl Res. 2016;8(5):2179-2188.
39. Davoodian M, Boroumand N, Bahar MM, Jafarian AH, Asadi M, Hashemy SI. Evaluation of serum level of substance P and tissue distribution of NK-1 receptor in breast cancer. Mol Biol Rep. 2019;46(1):1285-1293. [DOI:10.1007/s11033-019-04599-9] [PMID]
40. Gharaee N, Pourali L, Jafarian AH, Hashemy SI. Evaluation of serum level of substance P and tissue distribution of NK-1 receptor in endometrial cancer. Mol Biol Rep. 2018;45(6):2257-2262. [DOI:10.1007/s11033-018-4387-1] [PMID]
41. Lorestani S, Ghahremanloo A, Jangjoo A, Abedi M, Hashemy SI. Evaluation of serum level of substance P and tissue distribution of NK-1 receptor in colorectal cancer. Mol Biol Rep. 2020:47(5):3469-3474. [DOI:10.1007/s11033-020-05432-4] [PMID]
42. Jin Z, Olaru A, Yang J, Sato F, Cheng Y, Kan T, et al. Hypermethylation of tachykinin-1 is a potential biomarker in human esophageal cancer. Clinical cancer. Clin Cancer Res. 2007;13(21):6293-300. [DOI:10.1158/1078-0432.CCR-07-0818] [PMID]
43. Kishi H, Mishima HK, Sakamoto I, Yamashita U. Stimulation of retinal pigment epithelial cell growth by neuropeptides in vitro. Curr Eye Res. 1996;15(7):708-13. [DOI:10.3109/02713689609003452] [PMID]
44. Reddy BY, Greco SJ, Patel PS, Trzaska KA, Rameshwar P. RE-1-silencing transcription factor shows tumor-suppressor functions and negatively regulates the oncogenic TAC1 in breast cancer cells. Proceedings of the National Academy of Sciences. 2009;106(11):4408-13. [DOI:10.1073/pnas.0809130106] [PMID] [PMCID]
45. Campbell DE, Raftery N, Tustin R, Tustin NB, DeSilvio ML, Cnaan A, et al. Measurement of plasma-derived substance P: biological, methodological, and statistical considerations. Clin Vaccine Immunol. 2006;13(11):1197-1203. [DOI:10.1128/CVI.00174-06] [PMID] [PMCID]
46. Corbally N, Powell D, Tipton KF. The binding of endogenous and exogenous substance-P in human plasma. Biochem Pharmacol. 1990;39(7):1161-6. [DOI:10.1016/0006-2952(90)90257-L] [PMID]

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