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Antihormone treatment differentially regulates PSA secretion, PSMA expression and 68Ga–PSMA uptake in LNCaP cells

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Title: Antihormone treatment differentially regulates PSA secretion, PSMA expression and 68Ga–PSMA uptake in LNCaP cells
Authors: C. S. Mathy, T. Mayr, S. Kürpig, M. Meisenheimer, R. C. Dolscheid-Pommerich, B. Stoffel-Wagner, G. Kristiansen, M. Essler, M. H. Muders, R. A. Bundschuh
Source: J Cancer Res Clin Oncol
Publisher Information: Springer Science and Business Media LLC, 2021.
Publication Year: 2021
Subject Terms: Glutamate Carboxypeptidase II, Male, Secretory Pathway, Edetic Acid/analogs, Cell Line, Tumor [MeSH], Glutamate Carboxypeptidase II/metabolism [MeSH], Prostate-Specific Antigen/drug effects [MeSH], Prostatic Neoplasms/metabolism [MeSH], Prostatic Neoplasms/drug therapy [MeSH], Prostatic Neoplasms/pathology [MeSH], Androgen Antagonists/therapeutic use [MeSH], Adenocarcinoma/metabolism [MeSH], Male [MeSH], Adenocarcinoma/drug therapy [MeSH], Adenocarcinoma/pathology [MeSH], Edetic Acid/pharmacokinetics [MeSH], Antigens, Surface/genetics [MeSH], Positron Emission Tomography Computed Tomography/methods [MeSH], [, Glutamate Carboxypeptidase II/genetics [MeSH], Prostate cancer, Original Article – Cancer Research, PC-3 Cells [MeSH], Humans [MeSH], VPC-13566, Androstenes/therapeutic use [MeSH], Secretory Pathway/drug effects [MeSH], Prostate-specific membrane antigen, Antigens, Surface/metabolism [MeSH], Androgen Antagonists/pharmacology [MeSH], Androgen antagonist, Gene Expression Regulation, Neoplastic/drug effects [MeSH], Androstenes/pharmacology [MeSH], Oligopeptides/pharmacokinetics [MeSH], Adenocarcinoma/diagnosis [MeSH], Prostate-Specific Antigen/metabolism [MeSH], Prostatic Neoplasms/diagnosis [MeSH], Abiraterone, Prostatic Neoplasms, Androgen Antagonists, Gallium Radioisotopes, Adenocarcinoma, Prostate-Specific Antigen, 3. Good health, Gene Expression Regulation, Neoplastic, 03 medical and health sciences, 0302 clinical medicine, Cell Line, Tumor, Positron Emission Tomography Computed Tomography, Antigens, Surface, PC-3 Cells, Humans, Androstenes, Oligopeptides, Edetic Acid, Gallium Isotopes
Description: Background In recent years, a variety of innovative therapeutics for castration-resistant prostate cancer have been developed, including novel anti-androgenic drugs, such as abiraterone or VPC-13566. Therapeutic monitoring of these pharmaceuticals is performed either by measuring PSA levels in serum or by imaging. PET using PSMA ligands labeled with Fluor-18 or Gallium-68 is the most sensitive and specific imaging modality for detection of metastases in advanced prostate cancer. To date, it remains unclear how PSMA expression is modulated by anti-hormonal treatment and how it correlates with PSA secretion. Methods We analyzed modulation of PSMA-mRNA and protein expression, 68Ga–PSMA uptake and regulation of PSA secretion by abiraterone or VPC-13566 in LNCaP cells in vitro. Results We found that abiraterone and VPC-13566 upregulate PSMA protein and mRNA expression but block PSA secretion in LNCaP cells. Both anti-androgens also enhanced 68Ga–PSMA uptake normalized by the number of cells, whereas abiraterone and VPC-13566 reduced 68Ga–PSMA uptake in total LNCaP monolayers treated due to cell death. Conclusion Our data indicate that PSA secretion and PSMA expression are differentially regulated upon anti-androgen treatment. This finding might be important for the interpretation of 68Ga–PSMA PET images in monitoring therapies with abiraterone and VPC-13566 in prostate cancer patients, but needs to be validated in vivo.
Document Type: Article
Other literature type
Language: English
ISSN: 1432-1335
0171-5216
DOI: 10.1007/s00432-021-03583-w
Access URL: https://link.springer.com/content/pdf/10.1007/s00432-021-03583-w.pdf
https://pubmed.ncbi.nlm.nih.gov/33760944
https://europepmc.org/article/PMC/PMC8076114
https://www.ncbi.nlm.nih.gov/pubmed/33760944
https://link.springer.com/content/pdf/10.1007/s00432-021-03583-w.pdf
https://link.springer.com/article/10.1007/s00432-021-03583-w
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8076114
https://pubmed.ncbi.nlm.nih.gov/33760944/
https://repository.publisso.de/resource/frl:6449904
Rights: CC BY
URL: http://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (http://creativecommons.org/licenses/by/4.0/) .
Accession Number: edsair.doi.dedup.....c6fa28e5f68fce557b52d64da8b15053
Database: OpenAIRE
Description
Abstract:Background In recent years, a variety of innovative therapeutics for castration-resistant prostate cancer have been developed, including novel anti-androgenic drugs, such as abiraterone or VPC-13566. Therapeutic monitoring of these pharmaceuticals is performed either by measuring PSA levels in serum or by imaging. PET using PSMA ligands labeled with Fluor-18 or Gallium-68 is the most sensitive and specific imaging modality for detection of metastases in advanced prostate cancer. To date, it remains unclear how PSMA expression is modulated by anti-hormonal treatment and how it correlates with PSA secretion. Methods We analyzed modulation of PSMA-mRNA and protein expression, 68Ga–PSMA uptake and regulation of PSA secretion by abiraterone or VPC-13566 in LNCaP cells in vitro. Results We found that abiraterone and VPC-13566 upregulate PSMA protein and mRNA expression but block PSA secretion in LNCaP cells. Both anti-androgens also enhanced 68Ga–PSMA uptake normalized by the number of cells, whereas abiraterone and VPC-13566 reduced 68Ga–PSMA uptake in total LNCaP monolayers treated due to cell death. Conclusion Our data indicate that PSA secretion and PSMA expression are differentially regulated upon anti-androgen treatment. This finding might be important for the interpretation of 68Ga–PSMA PET images in monitoring therapies with abiraterone and VPC-13566 in prostate cancer patients, but needs to be validated in vivo.
ISSN:14321335
01715216
DOI:10.1007/s00432-021-03583-w