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Antihormone treatment differentially regulates PSA secretion, PSMA expression and 68 Ga-PSMA uptake in LNCaP cells.
Journal of Cancer Research and Clinical Oncology 2021 March 25
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, 68 Ga-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 68 Ga-PSMA uptake normalized by the number of cells, whereas abiraterone and VPC-13566 reduced 68 Ga-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 68 Ga-PSMA PET images in monitoring therapies with abiraterone and VPC-13566 in prostate cancer patients, but needs to be validated in vivo.
METHODS: We analyzed modulation of PSMA-mRNA and protein expression, 68 Ga-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 68 Ga-PSMA uptake normalized by the number of cells, whereas abiraterone and VPC-13566 reduced 68 Ga-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 68 Ga-PSMA PET images in monitoring therapies with abiraterone and VPC-13566 in prostate cancer patients, but needs to be validated in vivo.
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