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PSA Secretion from Single Circulating Tumor Cells of Metastatic Castration-Naïve Prostate Cancer Patients
Eshwari Dathathri1, Fikri Abali1, Michiel Stevens1,2
1Department of Medical Cell Biophysics, Technical Medical Center, Faculty of Science and Technology, University of Twente, Enschede, the Netherlands.
Cancer Research Communications
|July 31, 2025
Summary
Prostate-specific antigen (PSA) levels vary significantly between individual circulating tumor cells (CTCs) in metastatic prostate cancer patients. This heterogeneity explains why PSA is an unreliable biomarker for treatment response.
Area of Science:
- Oncology
- Biomarker Discovery
- Prostate Cancer Research
Background:
- Prostate-specific antigen (PSA) is a widely used biomarker for prostate cancer screening and monitoring.
- PSA levels can be modulated by therapies without reflecting true disease progression or antitumor effects.
- Circulating tumor cells (CTCs) offer a more objective measure of treatment response, but discrepancies with PSA levels exist.
Purpose of the Study:
- To investigate the heterogeneity of PSA secretion from individual CTCs in patients with metastatic castration-naïve prostate cancer (mCNPC).
- To understand how single-cell PSA secretion variability impacts the reliability of PSA as a biomarker.
Main Methods:
- Enrichment of CTCs from diagnostic leukapheresis of 18 therapy-naïve mCNPC patients using EpCAM-based immunomagnetic separation.
- Isolation and single-cell deposition of Calcein+ CD45- cells onto a nanowell array.
- Measurement of PSA secretion from individual CTCs over 24 hours.
Main Results:
- PSA secretion was detected in CTCs from 9 out of 18 patients.
- Between 29% and 100% of CTCs within a patient secreted PSA, with significant inter-patient and intra-patient heterogeneity.
- Observed average PSA secretion levels ranged from 4 to 11.68 pg/cell, with considerable variation.
Conclusions:
- Individual CTCs in mCNPC patients exhibit significant heterogeneity in PSA production, even before treatment.
- This variability in single-cell PSA secretion underscores the limitations of using PSA as a sole biomarker for assessing treatment response in prostate cancer.
