title: Recruited cells can become transformed and overtake PDGF-induced murine gliomas in vivo during tumor progression.
abstract: BACKGROUND
  Gliomas are thought to form by clonal expansion from a single cell-of-origin, and progression-associated mutations to occur in its progeny cells. Glioma progression is associated with elevated growth factor signaling and loss of function of tumor suppressors Ink4a, Arf and Pten. Yet, gliomas are cellularly heterogeneous; they recruit and trap normal cells during infiltration.
  
  
  RESULTS
  We performed lineage tracing in a retrovirally mediated, molecularly and histologically accurate mouse model of hPDGFb-driven gliomagenesis. We were able to distinguish cells in the tumor that were derived from the cell-of-origin from those that were not. Phenotypic, tumorigenic and expression analyses were performed on both populations of these cells. Here we show that during progression of hPDGFb-induced murine gliomas, tumor suppressor loss can expand the recruited cell population not derived from the cell-of-origin within glioma microenvironment to dominate regions of the tumor, with essentially no contribution from the progeny of glioma cell-of-origin. Moreover, the recruited cells can give rise to gliomas upon transplantation and passaging, acquire polysomal expression profiles and genetic aberrations typically present in glioma cells rather than normal progenitors, aid progeny cells in glioma initiation upon transplantation, and become independent of PDGFR signaling.
  
  
  CONCLUSIONS
  These results indicate that non-cell-of-origin derived cells within glioma environment in the mouse can be corrupted to become bona fide tumor, and deviate from the generally established view of gliomagenesis.
authors.affiliation: Department of Cancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York, New York, United States of America.
authors.forename: Elena I
authors.initials: EI
authors.lastname: Fomchenko
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Dougherty
authors.forename: Karim Y
authors.initials: KY
authors.lastname: Helmy
authors.forename: Amanda M
authors.initials: AM
authors.lastname: Katz
authors.forename: Alexander
authors.initials: A
authors.lastname: Pietras
authors.forename: Cameron
authors.initials: C
authors.lastname: Brennan
authors.forename: Jason T
authors.initials: JT
authors.lastname: Huse
authors.forename: Ana
authors.initials: A
authors.lastname: Milosevic
authors.forename: Eric C
authors.initials: EC
authors.lastname: Holland
mesh_terms: D000071916:AC133 Antigen; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D002465:Cell Movement; D002471:Cell Transformation, Neoplastic / Q000378:metabolism / Q000473:pathology*; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000235:genetics / Q000473:pathology*; D006023:Glycoproteins / Q000378:metabolism; D006720:Homozygote; D006801:Humans; D051379:Mice; D009368:Neoplasm Transplantation; D010455:Peptides / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000378:metabolism*; D017479:Receptors, Platelet-Derived Growth Factor / Q000378:metabolism; D015398:Signal Transduction; D025521:Tumor Suppressor Proteins / Q000378:metabolism
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D006023:Glycoproteins; D010455:Peptides; D010982:Platelet-Derived Growth Factor; D025521:Tumor Suppressor Proteins; D017479:Receptors, Platelet-Derived Growth Factor