Document Detail

Invasive glioblastoma cells acquire stemness and increased Akt activation.
MedLine Citation:
PMID:  20563248     Owner:  NLM     Status:  MEDLINE    
Glioblastoma multiforme (GBM) is the most frequent and most aggressive brain tumor in adults. The dismal prognosis is due to postsurgery recurrences arising from escaped invasive tumor cells. The signaling pathways activated in invasive cells are under investigation, and models are currently designed in search for therapeutic targets. We developed here an in vivo model of human invasive GBM in mouse brain from a GBM cell line with moderate tumorigenicity that allowed simultaneous primary tumor growth and dispersal of tumor cells in the brain parenchyma. This strategy allowed for the first time the isolation and characterization of matched sets of tumor mass (Core) and invasive (Inv) cells. Both cell populations, but more markedly Inv cells, acquired stem cell markers, neurosphere renewal ability, and resistance to rapamycin-induced apoptosis relative to parental cells. The comparative phenotypic analysis between Inv and Core cells showed significantly increased tumorigenicity in vivo and increased invasion with decreased proliferation in vitro for Inv cells. Examination of a large array of signaling pathways revealed extracellular signal-regulated kinase (Erk) down-modulation and Akt activation in Inv cells and an opposite profile in Core cells. Akt activation correlated with the increased tumorigenicity, stemness, and invasiveness, whereas Erk activation correlated with the proliferation of the cells. These results underscore complementary roles of the Erk and Akt pathways for GBM proliferation and dispersal and raise important implications for a concurrent inhibitory therapy.
Jennifer R Molina; Yuho Hayashi; Clifton Stephens; Maria-Magdalena Georgescu
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Neoplasia (New York, N.Y.)     Volume:  12     ISSN:  1476-5586     ISO Abbreviation:  Neoplasia     Publication Date:  2010 Jun 
Date Detail:
Created Date:  2010-06-21     Completed Date:  2010-09-21     Revised Date:  2013-05-29    
Medline Journal Info:
Nlm Unique ID:  100886622     Medline TA:  Neoplasia     Country:  Canada    
Other Details:
Languages:  eng     Pagination:  453-63     Citation Subset:  IM    
Department of Neuro-oncology, The University of Texas MD Anderson Cancer Center, 6767 Bertner Ave., Houston, TX 77030, USA.
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MeSH Terms
Astrocytes / cytology,  metabolism
Blotting, Western
Brain Neoplasms / metabolism,  pathology*
Cell Proliferation
Cells, Cultured
Disease Models, Animal*
Extracellular Signal-Regulated MAP Kinases / metabolism
Fluorescent Antibody Technique
Glioblastoma / metabolism,  pathology*
Immunoenzyme Techniques
Mice, SCID
Neoplasm Invasiveness
Neoplastic Stem Cells / metabolism,  pathology*
Neurons / metabolism,  pathology
Phosphatidylinositol 3-Kinases / metabolism
Proto-Oncogene Proteins c-akt / metabolism*
Signal Transduction
Xenograft Model Antitumor Assays
Grant Support
Reg. No./Substance:
EC 2.7.1.-/Phosphatidylinositol 3-Kinases; EC Proteins c-akt; EC Signal-Regulated MAP Kinases

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