Glioblastoma-derived tumorospheres identify a population of tumor stem-like cells with angiogenic potential and enhanced multidrug resistance phenotype

Andrea Salmaggi, Amerigo Boiardi, Maurizio Gelati, Annamaria Russo, Chiara Calatozzolo, Emilio Ciusani, Francesca Luisa Sciacca, Arianna Ottolina, Eugenio Agostino Parati, Catehina La Porta, Giulio Alessandri, Carlo Marras, Danilo Croci, Marco De Rossi

Research output: Contribution to journalArticlepeer-review


We investigated in vitro the properties of selected populations of cancer stem-like cells defined as tumorospheres that were obtained from human glioblastoma. We also assessed their potential and capability of differentiating into mature cells of the central nervous system. In vivo, their tumorigenicity was confirmed after transplantation into the brain of non-obese diabetic/severe combined immunodeficient (NOD-SCID) mice. The angiogenic potential of tumorospheres and glioblastoma-derived cells grown as adherent cells was revealed by evaluating the release of angiogenic factors such as vascular endothelial growth factor and CXCL12 by ELISA, as well as by rat aortic ring assay. The proliferative response of tumorospheres in the presence of CXCL12 was observed for the first time. Multidrug resistance-associated proteins 1 and 3 as well as other molecules conferring multidrug resistance were higher when compared with primary adherent cells derived from the same tumor. Finally, we obtained cells from the tumor developing after grafting that clearly expressed the putative neural stem cell marker GD133 as shown by FACS analysis and also nestin and CXCR4. The cells' positivity for glial fibrillary acidic protein was very low. Moreover these cells preserved their angiogenic potential. We conclude that human glioblastoma could contain tumor cell subsets with angiogenic and chemoresistance properties and that this chemoresistance potential is highly preserved by immature cells whereas the angiogenic potential is, to a higher extent, a property of mature cells. A better understanding of the features of these cell subsets may favor the development of more specifically targeted therapies.

Original languageEnglish
Pages (from-to)850-860
Number of pages11
Issue number8
Publication statusPublished - Dec 2006


  • Brain tumor stem-like cells
  • CXCL12
  • MDR proteins and adhesion molecules
  • VEGF

ASJC Scopus subject areas

  • Immunology


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