Summary
The methods used for detection of prostate cancer and prostate cancer lymph node metastases in medical diagnostics leave room for improvement. Currently, no means of identifying metastasized lymph nodes other than biopsies is available. Markers which are exclusively found on prostate cancer cells present a focal point for potential imaging methods. To complement the established markers like e.g. PCA3–a noncoding mRNA sequence–and PSA–a serine protease–we investigated the ectopically expressed G-protein coupled olfactory receptor OR1D2 as a possible target for prostate-specific detection with its agonist bourgeonal which has been conjugated to two different fluorescent dyes. We performed mRNA expression analysis of the OR1D2 receptor mRNA by reverse transcriptase polymerase chain reaction on LNCaP prostate carcinoma cells and three other non-prostate derived carcinoma cell lines. Additionally, we used flow cytometry to investigate the uptake of fluorescent-dye-bound OR1D2-ligand bourgeonal into the examined carcinoma cell lines. Finally, confocal laser scanning microscopy of in vitro cell culture and in vivo tumor xenografts on mice was performed. We could confirm OR1D2 receptor mRNA overexpression as well as stronger uptake of both bourgeonal conjugates in vitro and in vivo for LNCaP cells compared to the non-prostate derived cell lines. Cytoplasmic accumulation and no adverse effects after in vitro and in vivo application of the conjugates were observed. The conjugates represent a platform for the development of future prostate-specific imaging applications, e.g. detection of metastasized lymph nodes during surgery by intraoperative laser examination.
Similar content being viewed by others
References
Catalona WJ, Smith DS, Ratliff TL, Dodds KM, Coplen DE, Yuan JJ, Petros JA, Andriole GL (1991) Measurement of prostate-specific antigen in serum as a screening test for prostate cancer. N Engl J Med 324:1156–1161, Erratum in: (1991) N Engl J Med 325:1324
Djavan B, Eckersberger E, Finkelstein J, Sadri H, Taneja SS, Lepor H (2010) Prostate-specific antigen testing and prostate cancer screening. Prim Care 37:441–459, vii
Vosshall LB (2004) Olfaction: attracting both sperm and the nose. Curr Biol 14:R918–R920
Spehr M, Schwane K, Heilmann S, Gisselmann G, Hummel T, Hatt H (2004) Dual capacity of a human olfactory receptor. Curr Biol 14:R832–R833
Spehr M, Hatt H (2005) A potential role of odorant receptor agonists and antagonists in the treatment of infertility and contraception. Curr Opin Investig Drugs 6:364–368
Sturzu A, Echner H, Heckl S (2009) The lily-of-the-valley fragrance receptor–potential in prostate cancer imaging. Prostate 69:1599–1602
Cook BL, Steuerwald D, Kaiser L, Graveland-Bikker J, Vanberghem M, Berke AP, Herlihy K, Pick H, Vogel H, Zhang S (2009) Large-scale production and study of a synthetic G protein-coupled receptor: human olfactory receptor 17-4. Proc Natl Acad Sci U S A 106:11925–11930
Gottesman MM (2002) Mechanisms of cancer drug resistance. Annu Rev Med 53:615–627
Angelotti T, Daunt D, Shcherbakova OG, Kobilka B, Hurt CM (2010) Regulation of G-protein coupled receptor traffic by an evolutionary conserved hydrophobic signal. Traffic 11:560–578
Benchaib A, Delorme R, Pluvinage M, Bryon PA, Souchier C (1996) Evaluation of five green fluorescence-emitting streptavidin-conjugated fluorochromes for use in immunofluorescence microscopy. Histochem Cell Biol 106:253–256
Henry JB, Nakamura RM, Tucker ES, Carlson IH (1991) Immunoassays in the clinical laboratory. In: Henry JB (ed) Clinical diagnosis and management by laboratory methods. WB Saunders, Philadelphia, pp 870–871
Schilling D, de Reijke T, Tombal B, de la Taille A, Hennenlotter J, Stenzl A (2010) The prostate cancer gene 3 assay: indications for use in clinical practice. BJU Int 105(4):452–455
Acknowledgment
This study is supported by the Wilhelm Sander Foundation, the Hertie Foundation for Brain Research and the Interdisciplinary Center for Clinical Research, University of Tübingen.
Conflict of interest declaration
The authors declare that they have no conflict of interest.
Author information
Authors and Affiliations
Corresponding author
Additional information
Alexander Sturzu and Sumbla Sheikh contributed equally
Rights and permissions
About this article
Cite this article
Sturzu, A., Sheikh, S., Echner, H. et al. Novel bourgeonal fragrance conjugates for the detection of prostate cancer. Invest New Drugs 31, 1151–1157 (2013). https://doi.org/10.1007/s10637-013-9943-x
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10637-013-9943-x