Skip to main content

Advertisement

Log in

Increased expressions of cannabinoid receptor-1 and transient receptor potential vanilloid-1 in human prostate carcinoma

  • Original Paper
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

Purpose

Recently, functional cannabinoid receptor-1 (CB1) and vanilloid receptor-1 (TRPV1) have been described in human prostate and prostate cancer-derived cell lines where the activation of the receptors resulted in inhibition of cellular growth. We, however, lack the description of the expression of these molecules in human prostate cancer (PCC) and in benign prostate hyperplasia (BPH).

Methods

Therefore, immunohistochemistry, Western blotting, and quantitative “real-time Q-PCR were performed to define the expressions of CB1 and TRPV1 in healthy and diseased prostate tissues.

Results

CB1 was identified in epithelial and smooth muscle cells types of the human prostate, whereas TRPV1 was exclusively localized to the mucosal cells. We also found that the expression of CB1 and TRPV1 (both at the protein and mRNA levels) were significantly up-regulated in PCC. However, while the increased expression of TRPV1 showed a proper correlation with increasing PCC tumor grades, such phenomenon was not observed with CB1. In addition, we also measured markedly elevated CB1 levels in BPH tissues whilst the expression of TRPV1 was not altered when compared to healthy control prostate.

Conclusions

Our findings strongly argue for that (1) the CB1 and TRPV1 molecules as well as their ligands may indeed possess a promising future role in the treatment of PCC; (2) TRPV1 may also serve as a prognostic factor in PCC; and (3) CB1 may act as a potential target molecule in the therapeutic management of BPH.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Bodó E, Kovács I, Telek A, Varga A, Paus R, Kovács L et al (2004) Vanilloid receptor-1 is widely expressed on various epithelial and mesenchymal cell types of human skin. J Invest Dermatol 123:410–413. doi:10.1111/j.0022-202X.2004.23209.x

    Article  PubMed  Google Scholar 

  • Bodó E, Bíró T, Telek A, Czifra G, Griger Z, Tóth IB et al (2005) A “hot” new twist to hair biology: Involvement of vanilloid receptor-1 (VR1/TRPV1) signaling in human hair growth control. Am J Pathol 166:985–998

    PubMed  Google Scholar 

  • Casanova ML, Blazquez C, Martinez-Palacio J, Villanueva C, Fernandez-Acenero MJ, Huffman JW et al (2003) Inhibition of skin tumor growth and angiogenesis in vivo by activation of cannabinoid receptors. J Clin Invest 111:43–50

    PubMed  CAS  Google Scholar 

  • Caterina MJ, Julius D (2001) The vanilloid receptor: a molecular gateway to the pain pathway. Annu Rev Neurosci 24:487–517. doi:10.1146/annurev.neuro.24.1.487

    Article  PubMed  CAS  Google Scholar 

  • De Petrocellis L, Cascio MG, Di Marzo V (2004) The endocannabinoid system: a general view and latest additions. Br J Pharmacol 141:765–774. doi:10.1038/sj.bjp.0705666

    Article  PubMed  Google Scholar 

  • Di Marzo V, Bifulco M, De Petrocellis L (2004) The endocannabinoid system and its therapeutic exploitation. Nat Rev Drug Discov 3:7712–7784. doi:10.1038/nrd1495

    Google Scholar 

  • Fixemer T, Wissenbach U, Flockerzi V, Bonkhoff H (2003) Expression of the Ca2+-selective cation channel TRPV6 in human prostate cancer: a novel prognostic marker for tumor progression. Oncogene 22:7858–7861. doi:10.1038/sj.onc.1206895

    Article  PubMed  CAS  Google Scholar 

  • Galiegue S, Mary S, Marchand J, Dussossoy D, Carriere D, Carayon P et al (1995) Expression of central and peripheral cannabinoid receptors in human immune tissues and leukocyte subpopulations. Eur J Biochem 232:54–61. doi:10.1111/j.1432-1033.1995.tb20780.x

    Article  PubMed  CAS  Google Scholar 

  • Griger Z, Páyer E, Kovács I, Tóth IB, Kovács L, Sipka S et al (2007) Protein kinase Cβ and δ isoenzymes promote arachidonic acid production and proliferation of MonoMac-6 cells. J Mol Med 85:1031–1042. doi:10.1007/s00109-007-0209-y

    Article  PubMed  CAS  Google Scholar 

  • Lazzeri M, Vannucchi MG, Zardo C, Spinelli M, Beneforti P, Turini D et al (2004) Immunohistochemical evidence of vanilloid receptor 1 in normal human urinary bladder. Eur Urol 46:792–798. doi:10.1016/j.eururo.2004.08.007

    Article  PubMed  CAS  Google Scholar 

  • Lazzeri M, Vannucchi MG, Spinelli M, Bizzoco E, Beneforti P, Turini D et al (2005) Transient receptor potential vanilloid type 1 (TRPV1) expression changes from normal urothelium to transitional cell carcinoma of human bladder. Eur Urol 48:691–698. doi:10.1016/j.eururo.2005.05.018

    Article  PubMed  CAS  Google Scholar 

  • Mori A, Lehmann S, O’Kelly J, Kumagai T, Desmond JC, Pervan M et al (2006) Capsaicin, a component of red peppers, inhibits the growth of androgen-independent, p53 mutant prostate cancer cells. Cancer Res 66:3222–3229. doi:10.1158/0008-5472.CAN-05-0087

    Article  PubMed  CAS  Google Scholar 

  • Nithipatikom K, Endsley MP, Isbell MA, Falck JR, Iwamoto Y, Hillard CJ et al (2004) 2-Arachidonoylglycerol: a novel inhibitor of androgen-independent prostate cancer cell invasion. Cancer Res 64:8826–8830. doi:10.1158/0008-5472.CAN-04-3136

    Article  PubMed  CAS  Google Scholar 

  • Pacher P, Batkai S, Kunos G (2005) Cardiovascular pharmacology of cannabinoids. Handb Exp Pharmacol 168:599–625. doi:10.1007/3-540-26573-2_20

    Article  PubMed  CAS  Google Scholar 

  • Paus R, Schmelz M, Bíró T, Steinhoff M (2006) Frontiers in pruritus research: scratching the brain for more effective itch therapy. J Clin Invest 116:1174–1186. doi:10.1172/JCI28553

    Article  PubMed  CAS  Google Scholar 

  • Ruiz-Llorente L, Sanchez MG, Carmena MJ, Prieto JC, Sanchez-Chapado M, Izquierdo A et al (2003) Expression of functionally active cannabinoid receptor CB1 in the human prostate gland. Prostate 54:95–102. doi:10.1002/pros.10165

    Article  PubMed  CAS  Google Scholar 

  • Sanchez MG, Sanchez AM, Collado B, Malagarie-Cazenave S, Olea N, Carmena MJ et al (2005) Expression of the transient receptor potential vanilloid 1 (TRPV1) in LNCaP and PC-3 prostate cancer cells and in human prostate tissue. Eur J Pharmacol 515:20–27. doi:10.1016/j.ejphar.2005.04.010

    Article  PubMed  CAS  Google Scholar 

  • Sanchez AM, Sanchez MG, Malagarie-Cazenave S, Olea N, Diaz-Laviada I (2006) Induction of apoptosis in prostate tumor PC-3 cells and inhibition of xenograft prostate tumor growth by the vanilloid capsaicin. Apoptosis 11:89–99. doi:10.1007/s10495-005-3275-z

    Article  PubMed  CAS  Google Scholar 

  • Sarfaraz S, Afaq F, Adhami VM, Mukhtar H (2005) Cannabinoid receptor as a novel target for the treatment of prostate cancer. Cancer Res 65:1635–1641. doi:10.1158/0008-5472.CAN-04-3410

    Article  PubMed  CAS  Google Scholar 

  • Stein RJ, Santos S, Nagatomi J, Hayashi Y, Minnery BS, Xavier M et al (2004) Cool (TRPM8) and hot (TRPV1) receptors in the bladder and male genital tract. J Urol 712:1175–1178. doi:10.1097/01.ju.0000134880.55119.cf

    Article  Google Scholar 

  • Telek A, Bíró T, Bodó E, Tóth IB, Borbíró I, Kovács L et al (2007) Inhibition of human hair follicle growth by endo- and exocannabinoids. FASEB J 21:3534–3541. doi:10.1096/fj.06-7689com

    Article  PubMed  CAS  Google Scholar 

  • Varga A, Czifra G, Tállai B, Németh T, Kovács I, Kovács L et al (2004) Tumor grade-dependent alterations in the protein kinase C isoform pattern in urinary bladder carcinomas. Eur Urol 46:462–465

    PubMed  CAS  Google Scholar 

  • Xu X, Liu Y, Huang S, Liu G, Xie C, Zhou J et al (2006) Overexpression of cannabinoid receptors CB1 and CB2 correlates with improved prognosis of patients with hepatocellular carcinoma. Cancer Genet Cytogenet 171:31–38. doi:10.1016/j.cancergencyto.2006.06.014

    Article  PubMed  CAS  Google Scholar 

  • Zhang L, Barritt GJ (2006) TRPM8 in prostate cancer cells: a potential diagnostic and prognostic marker with a secretory function? Endocr Relat Cancer 13:27–38. doi:10.1677/erc.1.01093

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by Hungarian research grants: OTKA 63153, OTKA 49231, ETT 480/2006, ETT 482/2006, RET 06/2004. The authors state no competing financial interest. T.B. is a recipient of the János Bolyai research scholarship of the Hungarian Academy of Sciences.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Tamás Bíró.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Czifra, G., Varga, A., Nyeste, K. et al. Increased expressions of cannabinoid receptor-1 and transient receptor potential vanilloid-1 in human prostate carcinoma. J Cancer Res Clin Oncol 135, 507–514 (2009). https://doi.org/10.1007/s00432-008-0482-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00432-008-0482-3

Keywords

Navigation