| Full text | |
| Author(s): Show less - |
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]
Total Authors: 12
|
| Affiliation: | [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
Total Affiliations: 8
|
| Document type: | Journal article |
| Source: | ONCOTARGET; v. 7, n. 26, p. 40546-40557, JUN 28 2016. |
| Web of Science Citations: | 6 |
| 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. (AU) | |