title: Mesenchymal stem cell-like properties of CD133+ glioblastoma initiating cells.
abstract: Glioblastoma is composed of dividing tumor cells, stromal cells and tumor initiating CD133+ cells. Recent reports have discussed the origin of the glioblastoma CD133+ cells and their function in the tumor microenvironment. The present work sought to investigate the multipotent and mesenchymal properties of primary highly purified human CD133+ glioblastoma-initiating cells. To accomplish this aim, we used the following approaches: i) generation of tumor subspheres of CD133+ selected cells from primary cell cultures of glioblastoma; ii) analysis of the expression of pluripotency stem cell markers and mesenchymal stem cell (MSC) markers in the CD133+ glioblastoma-initiating cells; iii) side-by-side ultrastructural characterization of the CD133+ glioblastoma cells, MSC and CD133+ hematopoietic stem cells isolated from human umbilical cord blood (UCB); iv) assessment of adipogenic differentiation of CD133+ glioblastoma cells to test their MSC-like in vitro differentiation ability; and v) use of an orthotopic glioblastoma xenograft model in the absence of immune suppression. We found that the CD133+ glioblastoma cells expressed both the pluripotency stem cell markers (Nanog, Mush-1 and SSEA-3) and MSC markers. In addition, the CD133+ cells were able to differentiate into adipocyte-like cells. Transmission electron microscopy (TEM) demonstrated that the CD133+ glioblastoma-initiating cells had ultrastructural features similar to those of undifferentiated MSCs. In addition, when administered in vivo to non-immunocompromised animals, the CD133+ cells were also able to mimic the phenotype of the original patient's tumor. In summary, we showed that the CD133+ glioblastoma cells express molecular signatures of MSCs, neural stem cells and pluripotent stem cells, thus possibly enabling differentiation into both neural and mesodermal cell types.
authors.affiliation: Department of Neurology and Neurosurgery, Escola Paulista de Medicina-Universidade Federal de São Paulo (EPM-UNIFESP), São Paulo, Brazil.|Hospital Israelita Albert Einstein (HIAE), Experimental Research, São Paulo, Brazil.
authors.forename: Lorena Favaro
authors.initials: LF
authors.lastname: Pavon
authors.affiliation: Department of Neurology and Neurosurgery, Escola Paulista de Medicina-Universidade Federal de São Paulo (EPM-UNIFESP), São Paulo, Brazil.
authors.forename: Tatiana Tais
authors.initials: TT
authors.lastname: Sibov
authors.affiliation: Department of Genetics and Morphology, Universidade de Brasília, Brasília, Brazil.
authors.forename: Daniela Mara
authors.initials: DM
authors.lastname: de Oliveira
authors.affiliation: Hospital Israelita Albert Einstein (HIAE), Experimental Research, São Paulo, Brazil.|Allergy and Immunopathology Graduate Program, Faculdade de Medicina, Universidade de São Paulo (USP), São Paulo, Brazil.
authors.forename: Luciana C
authors.initials: LC
authors.lastname: Marti
authors.affiliation: Hospital Israelita Albert Einstein (HIAE), Experimental Research, São Paulo, Brazil.|Faculdade de Ciências Médicas da São Casa de São Paulo, São Paulo, Brazil.
authors.forename: Francisco Romero
authors.initials: FR
authors.lastname: Cabral
authors.affiliation: Biochemistry and Biophysics Laboratory, Butantan Institute, Neuro-Oncology Program, São Paulo, Brazil.
authors.forename: Jean Gabriel
authors.initials: JG
authors.lastname: de Souza
authors.affiliation: Biochemistry and Biophysics Laboratory, Butantan Institute, Neuro-Oncology Program, São Paulo, Brazil.
authors.forename: Pamela
authors.initials: P
authors.lastname: Boufleur
authors.affiliation: Department of Neurology and Neurosurgery, Escola Paulista de Medicina-Universidade Federal de São Paulo (EPM-UNIFESP), São Paulo, Brazil.|Hospital Israelita Albert Einstein (HIAE), Neuro-Oncology Program, São Paulo, Brazil.
authors.forename: Suzana M F
authors.initials: SM
authors.lastname: Malheiros
authors.affiliation: Department of Neurology and Neurosurgery, Escola Paulista de Medicina-Universidade Federal de São Paulo (EPM-UNIFESP), São Paulo, Brazil.
authors.forename: Manuel A
authors.initials: MA
authors.lastname: de Paiva Neto
authors.affiliation: Discipline of Nephrology, Escola Paulista de Medicina-Universidade Federal de São Paulo (EPM-UNIFESP), São Paulo, Brazil.
authors.forename: Edgard Ferreira
authors.initials: EF
authors.lastname: da Cruz
authors.affiliation: Biochemistry and Biophysics Laboratory, Butantan Institute, Neuro-Oncology Program, São Paulo, Brazil.
authors.forename: Ana Marisa
authors.initials: AM
authors.lastname: Chudzinski-Tavassi
authors.affiliation: Department of Neurology and Neurosurgery, Escola Paulista de Medicina-Universidade Federal de São Paulo (EPM-UNIFESP), São Paulo, Brazil.
authors.forename: Sérgio
authors.initials: S
authors.lastname: Cavalheiro
mesh_terms: D000071916:AC133 Antigen / Q000378:metabolism*; D017667:Adipocytes / Q000166:cytology; D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D001932:Brain Neoplasms / Q000378:metabolism*; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D005312:Fetal Blood / Q000166:cytology; D005909:Glioblastoma / Q000378:metabolism*; D006801:Humans; D016130:Immunophenotyping; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology; D008863:Microspheres; D014411:Neoplastic Stem Cells / Q000166:cytology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000071916:AC133 Antigen; D014408:Biomarkers, Tumor; C000606023:PROM1 protein, human
keywords: CD133+; TEM; neurospheres; tumorigenesis in vivo; MSC immunophenotype