title: Astrocyte-specific expression patterns associated with the PDGF-induced glioma microenvironment.
abstract: BACKGROUND
  The tumor microenvironment contains normal, non-neoplastic cells that may contribute to tumor growth and maintenance. Within PDGF-driven murine gliomas, tumor-associated astrocytes (TAAs) are a large component of the tumor microenvironment. The function of non-neoplastic astrocytes in the glioma microenvironment has not been fully elucidated; moreover, the differences between these astrocytes and normal astrocytes are unknown. We therefore sought to identify genes and pathways that are increased in TAAs relative to normal astrocytes and also to determine whether expression of these genes correlates with glioma behavior.
  
  
  RESULTS
  We compared the gene expression profiles of TAAs to normal astrocytes and found the Antigen Presentation Pathway to be significantly increased in TAAs. We then identified a gene signature for glioblastoma (GBM) TAAs and validated the expression of some of those genes within the tumor. We also show that TAAs are derived from the non-tumor, stromal environment, in contrast to the Olig2+ tumor cells that constitute the neoplastic elements in our model. Finally, we validate this GBM TAA signature in patients and show that a TAA-derived gene signature predicts survival specifically in the human proneural subtype of glioma.
  
  
  CONCLUSIONS
  Our data identifies unique gene expression patterns between populations of TAAs and suggests potential roles for stromal astrocytes within the glioma microenvironment. We show that certain stromal astrocytes in the tumor microenvironment express a GBM-specific gene signature and that the majority of these stromal astrocyte genes can predict survival in the human disease.
authors.affiliation: Biochemistry, Cell, and Molecular Biology Program, Weill Medical College of Cornell University, New York, New York, United States of America.
authors.forename: Amanda M
authors.initials: AM
authors.lastname: Katz
authors.forename: Nduka M
authors.initials: NM
authors.lastname: Amankulor
authors.forename: Ken
authors.initials: K
authors.lastname: Pitter
authors.forename: Karim
authors.initials: K
authors.lastname: Helmy
authors.forename: Massimo
authors.initials: M
authors.lastname: Squatrito
authors.forename: Eric C
authors.initials: EC
authors.lastname: Holland
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology*; D001932:Brain Neoplasms / Q000378:metabolism; D020869:Gene Expression Profiling; D005909:Glioblastoma / Q000378:metabolism; D005910:Glioma / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D018960:Hyaluronan Receptors / Q000096:biosynthesis; D007150:Immunohistochemistry / Q000379:methods; D051379:Mice; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence / Q000379:methods; D010982:Platelet-Derived Growth Factor / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D018960:Hyaluronan Receptors; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D049452:Green Fluorescent Proteins