title: Molecular analysis of CD133-positive circulating tumor cells from patients with metastatic castration-resistant prostate cancer.
abstract: The function and clinical utility of stem cell markers in metastatic castration-resistant prostate cancer (mCRPC) remains unresolved, and their expression may confer important therapeutic opportunities for staging and therapy. In the adult human prostate, CD133 (PROM1) expression identifies infrequent prostate epithelial progenitor cells and putative cancer stem cells. Previous work demonstrated an association with CD133 and cancer cell proliferation usingin vitromodel systems. The primary objective here was to investigate the expression of CD133 in circulating tumor cells (CTCs) from patients with mCRPC and to test the hypothesis that patients with mCRPC had CD133-positive CTCs associated with increased cell proliferation, changes in the androgen receptor (AR) protein expression, or AR nuclear co-localization. We utilized ImageStreamX technology, which combines flow cytometry and fluorescence microscopy, to capture and analyze CD45-negative/EpCAM-positive CTCs for CD133, Ki-67, and AR. All patient samples (20/20) contained CD133-positive populations of CTCs, and on average 50.9 ± 28.2% (range of 18.2% to 100%) of CTCs were CD133-positive. CD133-positive CTCs have increased Ki-67 protein expression compared to CD133-negative CTCs, implying that CD133-positive CTCs may have greater proliferative potential when compared to their CD133-negative counterparts. CD133-positive and CD133-negative CTCs have similar levels of AR protein expression and cellular co-localization with nuclear markers, implying that CD133 expression is independent of AR pathway activity and an AR-independent marker of mCRPC proliferation. These studies demonstrate the presence of CD133-positive populations in CTCs from mCRPC with increased proliferative potential.
authors.affiliation: Committee on Immunology, The University of Chicago, Chicago, IL, USA.
authors.forename: Edwin E
authors.initials: EE
authors.lastname: Reyes
authors.affiliation: Department of Medicine, Section of Hematology/Oncology, The University of Chicago, Chicago, IL, USA.
authors.forename: Marc
authors.initials: M
authors.lastname: Gillard
authors.affiliation: Flow Cytometry Facility, The University of Chicago, Chicago, IL, USA.
authors.forename: Ryan
authors.initials: R
authors.lastname: Duggan
authors.affiliation: Department of Public Health Sciences, The University of Chicago, Chicago, IL, USA.
authors.forename: Kristen
authors.initials: K
authors.lastname: Wroblewski
authors.affiliation: Committee on Cancer Biology, The University of Chicago, Chicago, IL, USA.
authors.forename: Steven
authors.initials: S
authors.lastname: Kregel
authors.affiliation: Department of Surgery, Section of Urology, The University of Chicago, Chicago, IL, USA.
authors.forename: Masis
authors.initials: M
authors.lastname: Isikbay
authors.affiliation: Department of Surgery, Section of Urology, The University of Chicago, Chicago, IL, USA.
authors.forename: Jacob
authors.initials: J
authors.lastname: Kach
authors.affiliation: Committee on Cancer Biology, The University of Chicago, Chicago, IL, USA.
authors.forename: Hannah
authors.initials: H
authors.lastname: Brechka
authors.affiliation: Department of Medicine, Section of Hematology/Oncology, The University of Chicago, Chicago, IL, USA.
authors.forename: David J Vander
authors.initials: DJ
authors.lastname: Weele
authors.affiliation: Department of Medicine, Section of Hematology/Oncology, The University of Chicago, Chicago, IL, USA.
authors.forename: Russell Z
authors.initials: RZ
authors.lastname: Szmulewitz
authors.affiliation: Committee on Cancer Biology, The University of Chicago, Chicago, IL, USA; Department of Surgery, Section of Urology, The University of Chicago, Chicago, IL, USA.
authors.forename: Donald J Vander
authors.initials: DJ
authors.lastname: Griend
keywords: CD133; androgen receptor; circulating tumor cells; metastatic castration-resistance prostate cancer; proliferation