title: Expression and prognostic significance of cancer stem cell markers CD24 and CD44 in urothelial bladder cancer xenografts and patients undergoing radical cystectomy.
abstract: OBJECTIVE
  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).
  
  
  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.affiliation: 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.
authors.forename: Thomas
authors.initials: T
authors.lastname: Hofner
authors.affiliation: Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany; Clinical Cooperation Unit Molecular Tumor Pathology, German Cancer Research Center, Heidelberg, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Macher-Goeppinger
authors.affiliation: Division of Stem Cells and Cancer, HI-STEM gGmbH, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Corinna
authors.initials: C
authors.lastname: Klein
authors.affiliation: Division of Stem Cells and Cancer, HI-STEM gGmbH, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Schillert
authors.affiliation: Division of Stem Cells and Cancer, HI-STEM gGmbH, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Eisen
authors.affiliation: Division of Stem Cells and Cancer, HI-STEM gGmbH, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Steve
authors.initials: S
authors.lastname: Wagner
authors.affiliation: Division of Stem Cells and Cancer, HI-STEM gGmbH, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Teresa
authors.initials: T
authors.lastname: Rigo-Watermeier
authors.affiliation: Division of Stem Cells and Cancer, HI-STEM gGmbH, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Irène
authors.initials: I
authors.lastname: Baccelli
authors.affiliation: Division of Stem Cells and Cancer, HI-STEM gGmbH, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Vogel
authors.affiliation: Division of Stem Cells and Cancer, HI-STEM gGmbH, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Trumpp
authors.affiliation: Division of Stem Cells and Cancer, HI-STEM gGmbH, German Cancer Research Center (DKFZ), Heidelberg, Germany. Electronic address: martin.sprick@hi-stem.de.
authors.forename: Martin R
authors.initials: MR
authors.lastname: Sprick
mesh_terms: D000368:Aged; D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D051927:CD24 Antigen / Q000378:metabolism*; D051928:CD47 Antigen / Q000378:metabolism*; D015331:Cohort Studies; D015653:Cystectomy; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism*; D008207:Lymphatic Metastasis; D008297:Male; D051379:Mice; D008875:Middle Aged; D015999:Multivariate Analysis; D009368:Neoplasm Transplantation; D011379:Prognosis; D046888:Tissue Array Analysis; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000601:surgery*; D019459:Urothelium / Q000378:metabolism* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D051927:CD24 Antigen; C497483:CD44 protein, human; D051928:CD47 Antigen; C497894:CD47 protein, human; D018960:Hyaluronan Receptors
keywords: Bladder cancer; CD24; CD44; CD47; Survival; Urothelial cancer