Expression and prognostic significance of cancer stem cell markers CD24 and CD44 in urothelial bladder cancer xenografts and patients undergoing radical cystectomy

Thomas Hofner, Stephan Macher-Goeppinger, Corinna Klein, Anja Schillert, Christian Eisen, Steve Wagner, Teresa Rigo-Watermeier, Irène Baccelli, Vanessa Vogel, Andreas Trumpp, Martin R. Sprick

Research output: Contribution to journalArticle

20 Citations (Scopus)

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 CD24low- and CD24high- 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. CD24high/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.

Original languageEnglish (US)
Pages (from-to)678-686
Number of pages9
JournalUrologic Oncology: Seminars and Original Investigations
Volume32
Issue number5
DOIs
StatePublished - Jul 2014

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Neoplastic Stem Cells
Cystectomy
Heterografts
Urinary Bladder Neoplasms
Survival
Neoplasms
Multivariate Analysis
Staining and Labeling
Urothelium
Stromal Cells
Population
Flow Cytometry
Lymph Nodes

Keywords

  • Bladder cancer
  • CD24
  • CD44
  • CD47
  • Survival
  • Urothelial cancer

ASJC Scopus subject areas

  • Oncology
  • Urology

Cite this

Expression and prognostic significance of cancer stem cell markers CD24 and CD44 in urothelial bladder cancer xenografts and patients undergoing radical cystectomy. / Hofner, Thomas; Macher-Goeppinger, Stephan; Klein, Corinna; Schillert, Anja; Eisen, Christian; Wagner, Steve; Rigo-Watermeier, Teresa; Baccelli, Irène; Vogel, Vanessa; Trumpp, Andreas; Sprick, Martin R.

In: Urologic Oncology: Seminars and Original Investigations, Vol. 32, No. 5, 07.2014, p. 678-686.

Research output: Contribution to journalArticle

Hofner, Thomas ; Macher-Goeppinger, Stephan ; Klein, Corinna ; Schillert, Anja ; Eisen, Christian ; Wagner, Steve ; Rigo-Watermeier, Teresa ; Baccelli, Irène ; Vogel, Vanessa ; Trumpp, Andreas ; Sprick, Martin R. / Expression and prognostic significance of cancer stem cell markers CD24 and CD44 in urothelial bladder cancer xenografts and patients undergoing radical cystectomy. In: Urologic Oncology: Seminars and Original Investigations. 2014 ; Vol. 32, No. 5. pp. 678-686.
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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 CD24low- and CD24high- 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. CD24high/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.",
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T1 - Expression and prognostic significance of cancer stem cell markers CD24 and CD44 in urothelial bladder cancer xenografts and patients undergoing radical cystectomy

AU - Hofner, Thomas

AU - Macher-Goeppinger, Stephan

AU - Klein, Corinna

AU - Schillert, Anja

AU - Eisen, Christian

AU - Wagner, Steve

AU - Rigo-Watermeier, Teresa

AU - Baccelli, Irène

AU - Vogel, Vanessa

AU - Trumpp, Andreas

AU - Sprick, Martin R.

PY - 2014/7

Y1 - 2014/7

N2 - 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 CD24low- and CD24high- 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. CD24high/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.

AB - 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 CD24low- and CD24high- 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. CD24high/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.

KW - Bladder cancer

KW - CD24

KW - CD44

KW - CD47

KW - Survival

KW - Urothelial cancer

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