TY - JOUR
T1 - Why are systemic glioblastoma metastases rare? Systemic and cerebral growth of mouse glioblastoma
AU - Mourad, Pierre D.
AU - Farrell, Lindi
AU - Stamps, Louis D.
AU - Chicoine, Michael R.
AU - Silbergeld, Daniel L.
N1 - Funding Information:
This work was supported in part by The McDonnell Center for Cellular and Molecular Biology Award 26275D (DLS), and by the following awards from the National Institutes of Health: KO8 NS01730 (DLS), R29 NS69640 (DLS), K25 NS02234-01 (PDM), and NS 67493 (MRC). The authors are indebted to Michael Lai, PhD, of the Department of Microbiology at the University of Southern California for generously providing the DBT cell line, to Alex Spence, MD, of the University of Washington, and to an anonymous reviewer for constructive and thought-provoking comments.
PY - 2005/6
Y1 - 2005/6
N2 - 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.
AB - 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.
KW - DBT cell line
KW - Glioblastoma
KW - Glioma
KW - Invasion
KW - Metastasis
KW - Mice
UR - http://www.scopus.com/inward/record.url?scp=20344378933&partnerID=8YFLogxK
U2 - 10.1016/j.surneu.2004.08.062
DO - 10.1016/j.surneu.2004.08.062
M3 - Article
C2 - 15936366
AN - SCOPUS:20344378933
VL - 63
SP - 511
EP - 519
JO - Surgical Neurology
JF - Surgical Neurology
SN - 0090-3019
IS - 6
ER -