Abstract
PurposeOver 90% of all cancer related deaths are due to metastasis. However, current diagnostic tools can't reliably discriminate between invasive and localized cancers. Patients and methodsIn this proof-of-concept study, we employed the embryonic stem cell marker TRA-1-60 (TRA+) to identify TRA + cells within the blood of prostate cancer patients and searched for TRA + cells in men with metastatic and localized cancers. We isolated whole peripheral blood mononuclear cells from 26 metastatic prostate cancer patients, from 13 patients with localized prostate cancer and from 17 healthy controls. Cells were stained for DAPI, CD45 and TRA + by immunofluorescence and imaged by epi-fluorescence microscopy. Imaged-based software was used both to identify TRA + cells, and to analyze CD45 levels in TRA+ and negative cells. ResultsWe found high numbers of TRA + cells within the blood of metastatic cancer patients, whereas healthy individuals or men with localized prostate cancer showed none or very low numbers of TRA + cells. Further analysis of the CD45 levels of TRA + cells revealed a small population of TRA + cells with almost undetectable CD45 levels that were found frequently in metastatic prostate cancer patients. By excluding CD45 positive cells from the TRA + cell pool, we were able to refine the assay to be highly specific in identifying men with metastatic disease. In fact, the difference of CD45 levels between TRA+ and negative cells was a robust measure to distinguish between men with localized and metastatic prostate cancers in this small patient cohort. ConclusionsThe data suggest that metastatic prostate cancer patient have significant numbers of TRA+/CD45low cells which might represent a potential tool for diagnostic assessment in the future.
Highlights
Metastatic spread from the primary tumor to a distant organ site is the leading cause of cancer-related deaths
PBMC were incubated with CD45-FITC and TRA negative (TRA-)1-60 (Life technologies, 1:50) in blocking at 4 C overnight and stained with Alexa Fluor®594 Anti-Mouse (Thermo Fisher, 1:200) for 1 h at room temperature (RT)
We found a small population of TRA þ cells that had very low CD45 levels which was only present in metastatic prostate cancer patients (Figure 3A, box) and in the one patient who progressed to metastatic prostate cancer
Summary
Metastatic spread from the primary tumor to a distant organ site is the leading cause of cancer-related deaths. Despite primary treatment with either or both modalities a substantial number of men will develop metastatic disease. As in other solid tumors, the ability to predict disease progression with a simple blood test would be of great utility, both for diagnostic reasons and as a powerful surveillance tool. Such an assay would provide clinicians with a tool to identify patients with malignant disease progression at an earlier time point when treatment efforts are more effective
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