Why are systemic glioblastoma metastases rare? Systemic and cerebral growth of mouse glioblastoma.
BACKGROUND
Systemic metastasis of glioblastoma multiforme (GBM) in the form of bulk tumor is rare. This could be because of patient death before clinically detectable systemic metastasis, impediments to systemic egress, or the inability of GBM to grow outside the central nervous system (CNS). In the present paper, we tested this last hypothesis.


METHODS
The delayed brain tumor (DBT) cell was characterized with respect to in vitro and in vivo morphology, growth rate, anchorage-independent growth, glial fibrillary acidic protein expression and cytogenetic analysis, and major histocompatibility complex (MHC) typing. We then assayed implantation-induced intracerebral and systemic GBM growth using 3 rodent models with increasing relative immunologic differences between implanted DBT cells and hosts (Balb/c mice, an isograft, MHC I H2, class type D; C3H mice, an allograft; Wistar rats, a xenograft).


RESULTS
After implantation in the brain, DBT cells generated tumors that were similar to human GBM. Intracerebral DBT implantation as an isograft or allograft produced only intracranial tumors, whereas intracerebral and systemic implantation as a xenograft produced no tumors. Systemic isograft implantation yielded only systemic tumors. Systemic implantation as allografts produced only transient subcutaneous masses.


CONCLUSIONS
Delayed brain tumor cells implanted outside the CNS formed tumors unless there was a significant difference between the immunotype of the implanted cells and host. These results support the hypothesis that the rarity of systemic GBM tumors lies in the presence of physical barriers and/or systemic hurdles that prevent their timely growth. These results also demonstrate that GBMs are antigenic, although not immunogenic, with their syngeneic host. Therefore, GBM may be amenable to targeted immunotherapy given successful artificial priming of the immune system.
Mourad
Pierre D
PD
Department of Neurological Surgery, University of Washington, Seattle, WA 98195-6470, USA.
Farrell
Lindi
L
Stamps
Louis D
LD
Chicoine
Michael R
MR
Silbergeld
Daniel L
DL
D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D014408:Biomarkers, Tumor / Q000276:immunology; D001932:Brain Neoplasms / Q000276:immunology / Q000503:physiopathology*; D002540:Cerebral Cortex / Q000276:immunology / Q000473:pathology / Q000601:surgery; D004195:Disease Models, Animal; D005909:Glioblastoma / Q000276:immunology / Q000503:physiopathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008819:Mice, Nude; D009361:Neoplasm Invasiveness / Q000276:immunology; D009362:Neoplasm Metastasis / Q000276:immunology / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D023001:Transplantation Tolerance / Q000276:immunology; D014183:Transplantation, Heterologous / Q000276:immunology; D014184:Transplantation, Homologous / Q000276:immunology; D014185:Transplantation, Isogeneic / Q000276:immunology; D014407:Tumor Cells, Cultured
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor