Journal article
Pharmacological upregulation of prostate-specific membrane antigen (PSMA) expression in prostate cancer cells.
- Kranzbühler B Department of Urology, Laboratory for Tissue Engineering and Stem Cell Therapy, University Hospital Zürich, Zürich, Switzerland.
- Salemi S Department of Urology, Laboratory for Tissue Engineering and Stem Cell Therapy, University Hospital Zürich, Zürich, Switzerland.
- Umbricht CA Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Paul Scherrer Institut, Villigen-PSI, Switzerland.
- Müller C Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Paul Scherrer Institut, Villigen-PSI, Switzerland.
- Burger IA Department of Nuclear Medicine, University Hospital of Zürich, Zürich, Switzerland.
- Sulser T Department of Urology, Laboratory for Tissue Engineering and Stem Cell Therapy, University Hospital Zürich, Zürich, Switzerland.
- Eberli D Department of Urology, Laboratory for Tissue Engineering and Stem Cell Therapy, University Hospital Zürich, Zürich, Switzerland.
- 2018-04-11
Published in:
- The Prostate. - 2018
177Lu-PSMA-617
androgen antagonist
androgen receptor
prostate cancer
prostate-specific membrane antigen
Antigens, Surface
Antineoplastic Agents
Cell Line, Tumor
Cell Proliferation
Cell Survival
Glutamate Carboxypeptidase II
Humans
Male
Prostate
Prostatic Neoplasms
Up-Regulation
English
BACKGROUND
Prostate-specific membrane antigen (PSMA)-based imaging and therapy are increasingly used for prostate cancer management. However, limitations are a low PSMA expression in certain patients. Androgen receptor axis inhibition can induce PSMA expression in vitro. We hypothesized that different approved compounds upregulate PSMA expression and tested their effect in vitro.
METHODS
Androgen receptor (AR) expressing prostate cancer (LNCaP) and epithelial prostate cells (PNT1A) were treated for 7 days with enzalutamide, dutasteride, rapamycin, metformin, lovastatin, and acetylsalicylic acid (ASA). PSMA and AR protein expression was assessed using flow cytometry, immunocytochemistry and immunoblotting. Furthermore, uptake and internalization of 177 Lu-PSMA-617 was performed.
RESULTS
Enzalutamide and dutasteride led to a significant (both P < 0.05) upregulation of PSMA surface levels in LNCaP cells. In addition, treatment with rapamycin showed a non-significant trend toward PSMA upregulation. No changes were detected after treatment with vehicle, metformin, lovastatin, and ASA. Total PSMA protein expression was significantly enhanced after treatment with enzalutamide and rapamycin (both P < 0.05), whereas dutasteride led to a non-significant upregulation. Uptake of 177 Lu-PSMA-617 was significantly increased after treatment of LNCaP with enzalutamide, dutasteride, and rapamycin (P < 0.05). In addition, internalization was significantly increased by enzalutamide and rapamycin (P < 0.05), and non-significantly increased by dutasteride.
CONCLUSION
In conclusion, our data provide new insights into the effect of different approved pharmacological compounds that can markedly upregulate PSMA expression and radioligand uptake in vitro. Pharmacologically induced PSMA expression may prove useful to improve prostate cancer detection and to enhance anticancer effects in PSMA-based therapy.
Prostate-specific membrane antigen (PSMA)-based imaging and therapy are increasingly used for prostate cancer management. However, limitations are a low PSMA expression in certain patients. Androgen receptor axis inhibition can induce PSMA expression in vitro. We hypothesized that different approved compounds upregulate PSMA expression and tested their effect in vitro.
METHODS
Androgen receptor (AR) expressing prostate cancer (LNCaP) and epithelial prostate cells (PNT1A) were treated for 7 days with enzalutamide, dutasteride, rapamycin, metformin, lovastatin, and acetylsalicylic acid (ASA). PSMA and AR protein expression was assessed using flow cytometry, immunocytochemistry and immunoblotting. Furthermore, uptake and internalization of 177 Lu-PSMA-617 was performed.
RESULTS
Enzalutamide and dutasteride led to a significant (both P < 0.05) upregulation of PSMA surface levels in LNCaP cells. In addition, treatment with rapamycin showed a non-significant trend toward PSMA upregulation. No changes were detected after treatment with vehicle, metformin, lovastatin, and ASA. Total PSMA protein expression was significantly enhanced after treatment with enzalutamide and rapamycin (both P < 0.05), whereas dutasteride led to a non-significant upregulation. Uptake of 177 Lu-PSMA-617 was significantly increased after treatment of LNCaP with enzalutamide, dutasteride, and rapamycin (P < 0.05). In addition, internalization was significantly increased by enzalutamide and rapamycin (P < 0.05), and non-significantly increased by dutasteride.
CONCLUSION
In conclusion, our data provide new insights into the effect of different approved pharmacological compounds that can markedly upregulate PSMA expression and radioligand uptake in vitro. Pharmacologically induced PSMA expression may prove useful to improve prostate cancer detection and to enhance anticancer effects in PSMA-based therapy.
- Language
-
- English
- Open access status
- closed
- Identifiers
-
- DOI 10.1002/pros.23522
- PMID 29633296
- Persistent URL
- https://sonar.ch/global/documents/7259
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