CD133 positive embryonal rhabdomyosarcoma stem-like cell population is enriched in rhabdospheres

Autor: Ivo Leuschner, Carole Gengler, Felix Niggli, Valentina D'Alessandro, Beat Bornhauser, Beat W. Schäfer, Ewa Koscielniak, Sampoorna Satheesha, Michele Bernasconi, Susanne Oesch, Dagmar Walter, Hubert Rehrauer, Holger Moch, Patrick Albrecht
Rok vydání: 2011
Předmět:
Cellular differentiation
Cell Culture Techniques
lcsh:Medicine
Pediatrics
Mice
0302 clinical medicine
Basic Cancer Research
Rhabdomyosarcoma
Embryonal
AC133 Antigen
Rhabdomyosarcoma
lcsh:Science
0303 health sciences
education.field_of_study
Multidisciplinary
Cell Differentiation
Prognosis
3. Good health
Survival Rate
Oncology
030220 oncology & carcinogenesis
embryonic structures
Neoplastic Stem Cells
Medicine
Stem cell
Research Article
Homeobox protein NANOG
Histology
Transplantation
Heterologous
Population
Biology
03 medical and health sciences
SOX2
Antigens
CD
Cancer stem cell
Cell Line
Tumor
Biomarkers
Tumor
medicine
Animals
Humans
education
Glycoproteins
030304 developmental biology
Gene Expression Profiling
lcsh:R
medicine.disease
Molecular biology
Tissue Array Analysis
Pediatric Oncology
Cancer research
lcsh:Q
Embryonal rhabdomyosarcoma
Peptides
Developmental Biology
Zdroj: PloS one
PLoS ONE, Vol 6, Iss 5, p e19506 (2011)
PLoS ONE
DOI: 10.1371/journal.pone.0019506
Popis: Cancer stem cells (CSCs) have been identified in a number of solid tumors, but not yet in rhabdomyosarcoma (RMS), the most frequently occurring soft tissue tumor in childhood. Hence, the aim of this study was to identify and characterize a CSC population in RMS using a functional approach. We found that embryonal rhabdomyosarcoma (eRMS) cell lines can form rhabdomyosarcoma spheres (short rhabdospheres) in stem cell medium containing defined growth factors over several passages. Using an orthotopic xenograft model, we demonstrate that a 100 fold less sphere cells result in faster tumor growth compared to the adherent population suggesting that CSCs were enriched in the sphere population. Furthermore, stem cell genes such as oct4, nanog, c-myc, pax3 and sox2 are significantly upregulated in rhabdospheres which can be differentiated into multiple lineages such as adipocytes, myocytes and neuronal cells. Surprisingly, gene expression profiles indicate that rhabdospheres show more similarities with neuronal than with hematopoietic or mesenchymal stem cells. Analysis of these profiles identified the known CSC marker CD133 as one of the genes upregulated in rhabdospheres, both on RNA and protein levels. CD133(+) sorted cells were subsequently shown to be more tumorigenic and more resistant to commonly used chemotherapeutics. Using a tissue microarray (TMA) of eRMS patients, we found that high expression of CD133 correlates with poor overall survival. Hence, CD133 could be a prognostic marker for eRMS. These experiments indicate that a CD133(+) CSC population can be enriched from eRMS which might help to develop novel targeted therapies against this pediatric tumor.
Databáze: OpenAIRE
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