Thomas Hofner1, Stephan Macher-Goeppinger2, Corinna Klein3, Anja Schillert3, Christian Eisen3, Steve Wagner3, Teresa Rigo-Watermeier3, Irène Baccelli3, Vanessa Vogel3, Andreas Trumpp3, Martin R Sprick4. 1. Division of Stem Cells and Cancer, HI-STEM gGmbH, German Cancer Research Center (DKFZ), Heidelberg, Germany; Department of Urology, University Hospital Heidelberg, Heidelberg, Germany. Electronic address: kontakt@thomashoefner.de. 2. Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany; Clinical Cooperation Unit Molecular Tumor Pathology, German Cancer Research Center, Heidelberg, Germany. 3. Division of Stem Cells and Cancer, HI-STEM gGmbH, German Cancer Research Center (DKFZ), Heidelberg, Germany. 4. Division of Stem Cells and Cancer, HI-STEM gGmbH, German Cancer Research Center (DKFZ), Heidelberg, Germany. Electronic address: martin.sprick@hi-stem.de.
Abstract
OBJECTIVES: To evaluate CD24/CD44/CD47 cancer stem cell marker expressions in bladder cancer (BCa) and provide data on their prognostic significance for clinical outcome in patients undergoing radical cystectomy (RC). MATERIAL AND METHODS: Primary BCa tissue was used for xenograft studies. A tissue microarray was prepared using specimens from a cohort of 132 patients. All patients underwent RC for urothelial BCa between 2001 and 2010. Expression of CD24, CD44, and CD47 was examined in primary samples and xenografts by fluorescence-activated cell sorting. Populations of CD24(low)- and CD24(high)-expressing cells were sorted and evaluated for tumorigenicity in vivo. Tissue microarray was analyzed for CD24/CD44 staining intensity and tumor-specific vs. stromal cell staining. Associations with BCa survival, BCa stage, and lymph node status were evaluated by univariate and multivariate analyses. RESULTS: CD24 and CD44/CD47 expressions mark distinct cell populations within the normal urothelium as well as in BCa. CD24(high/low) expression was not sufficient to characterize CD24 as a BCa-initiating marker in in vivo primary xenotransplants. CD24 and CD44 expressions correlated with lower cancer-specific survival in patients. However, multivariate analyses of CD24 or CD44 did not demonstrate significantly increased hazards for cancer-specific death if analyzed together with stage, grade, and nodal status of patients. CONCLUSIONS: Cancer stem cell markers CD24/CD44/CD47 are differentially expressed in cells of urothelial BCa in patients undergoing RC and influence cancer-specific survival of patients. Further evaluation of CD24/CD44/CD47 protein expression could be of high therapeutic value in BCa. However, both CD24 and CD44 expressions cannot be regarded as independent prognostic parameters for patients undergoing RC.
OBJECTIVES: To evaluate CD24/CD44/CD47cancer stem cell marker expressions in bladder cancer (BCa) and provide data on their prognostic significance for clinical outcome in patients undergoing radical cystectomy (RC). MATERIAL AND METHODS: Primary BCa tissue was used for xenograft studies. A tissue microarray was prepared using specimens from a cohort of 132 patients. All patients underwent RC for urothelial BCa between 2001 and 2010. Expression of CD24, CD44, and CD47 was examined in primary samples and xenografts by fluorescence-activated cell sorting. Populations of CD24(low)- and CD24(high)-expressing cells were sorted and evaluated for tumorigenicity in vivo. Tissue microarray was analyzed for CD24/CD44 staining intensity and tumor-specific vs. stromal cell staining. Associations with BCa survival, BCa stage, and lymph node status were evaluated by univariate and multivariate analyses. RESULTS:CD24 and CD44/CD47 expressions mark distinct cell populations within the normal urothelium as well as in BCa. CD24(high/low) expression was not sufficient to characterize CD24 as a BCa-initiating marker in in vivo primary xenotransplants. CD24 and CD44 expressions correlated with lower cancer-specific survival in patients. However, multivariate analyses of CD24 or CD44 did not demonstrate significantly increased hazards for cancer-specific death if analyzed together with stage, grade, and nodal status of patients. CONCLUSIONS:Cancer stem cell markers CD24/CD44/CD47 are differentially expressed in cells of urothelial BCa in patients undergoing RC and influence cancer-specific survival of patients. Further evaluation of CD24/CD44/CD47 protein expression could be of high therapeutic value in BCa. However, both CD24 and CD44 expressions cannot be regarded as independent prognostic parameters for patients undergoing RC.
Authors: David B Thompson; Larry E Siref; Michael P Feloney; Ralph J Hauke; Devendra K Agrawal Journal: Expert Rev Clin Immunol Date: 2014-11-13 Impact factor: 4.473
Authors: Brian M Shinder; Adam Shupe; Geun Taek Lee; Mark N Stein; Isaac Y Kim; Eric A Singer Journal: Transl Cancer Res Date: 2018-08 Impact factor: 1.241
Authors: Margaretha A Skowron; Günter Niegisch; Gerhard Fritz; Tanja Arent; Joep G H van Roermund; Andrea Romano; Peter Albers; Wolfgang A Schulz; Michèle J Hoffmann Journal: J Exp Clin Cancer Res Date: 2015-11-25