A syngeneic glioma model to assess the impact of neural progenitor target cell age on tumor malignancy.
Human glioma incidence, malignancy, and treatment resistance are directly proportional to patient age. Cell intrinsic factors are reported to contribute to human age-dependent glioma malignancy, but suitable animal models to examine the role of aging are lacking. Here, we developed an orthotopic syngeneic glioma model to test the hypothesis that the age of neural progenitor cells (NPCs), presumed cells of glioma origin, influences glioma malignancy. Gliomas generated from transformed donor 3-, 12-, and 18-month-old NPCs in same-aged adult hosts formed highly invasive glial tumors that phenocopied the human disease. Survival analysis indicated increased malignancy of gliomas generated from older 12- and 18-month-old transformed NPCs compared with their 3-month counterparts (median survival of 38.5 and 42.5 vs. 77 days, respectively). This study showed for the first time that age of target cells at the time of transformation can affect malignancy and demonstrated the feasibility of a syngeneic model using transformed NPCs for future examination of the relative impacts of age-related cell intrinsic and cell-extrinsic factors in glioma malignancy.
Mikheev
Andrei M
AM
Department of Neurological Surgery, University of Washington School of Medicine, Seattle, 98195, USA.
Stoll
Elizabeth A
EA
Mikheeva
Svetlana A
SA
Maxwell
John-Patrick
JP
Jankowski
Pawel P
PP
Ray
Sutapa
S
Uo
Takuma
T
Morrison
Richard S
RS
Horner
Philip J
PJ
Rostomily
Robert C
RC
D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival; D016922:Cellular Senescence; D005910:Glioma / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism