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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Mesenchymal stem cell-like properties of CD133(+) glioblastoma-initiating cells

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Autor(es):
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Pavon, Lorena Favaro [1, 2] ; Sibov, Tatiana Tais [2] ; de Oliveira, Daniela Mara [3] ; Marti, Luciana C. [1, 4] ; Cabral, Francisco Romero [1, 5] ; de Souza, Jean Gabriel [6] ; Boufleur, Pamela [6] ; Malheiros, Suzana M. F. [2, 7] ; de Paiva Neto, Manuel A. [2] ; da Cruz, Edgard Ferreira [8] ; Chudzinski-Tavassi, Ana Marisa [6] ; Cavalheiro, Sergio [2]
Número total de Autores: 12
Afiliação do(s) autor(es):
[1] Hosp Israelita Albert Einstein, Expt Res, Sao Paulo - Brazil
[2] Univ Fed Sao Paulo, Escola Paulista Med, Dept Neurol & Neurosurg, UNIFESP, Sao Paulo - Brazil
[3] Univ Brasilia, Dept Genet & Morphol, Brasilia, DF - Brazil
[4] Univ Sao Paulo, Fac Med, Allergy & Immunopathol Grad Program, Sao Paulo - Brazil
[5] Fac Ciencias Med Sao Casa Sao Paulo, Sao Paulo - Brazil
[6] Butantan Inst, Neurooncol Program, Biochem & Biophys Lab, Sao Paulo - Brazil
[7] Hosp Israelita Albert Einstein, Neurooncol Program, Sao Paulo - Brazil
[8] Univ Fed Sao Paulo, Escola Paulista Med, Discipline Nephrol, UNIFESP, Sao Paulo - Brazil
Número total de Afiliações: 8
Tipo de documento: Artigo Científico
Fonte: ONCOTARGET; v. 7, n. 26, p. 40546-40557, JUN 28 2016.
Citações Web of Science: 6
Resumo

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. (AU)

Processo FAPESP: 11/50542-9 - Estudo das neuroesferas de glioblastoma humano e a relação quimiotática com células-tronco mesenquimais
Beneficiário:Lorena Favaro Pavon Porfirio
Linha de fomento: Auxílio à Pesquisa - Regular