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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Acta+Neuropathol
2014 ; 127
(6
): 897-909
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Human pontine glioma cells can induce murine tumors
#MMPMID24777482
Caretti V
; Sewing AC
; Lagerweij T
; Schellen P
; Bugiani M
; Jansen MH
; van Vuurden DG
; Navis AC
; Horsman I
; Vandertop WP
; Noske DP
; Wesseling P
; Kaspers GJ
; Nazarian J
; Vogel H
; Hulleman E
; Monje M
; Wurdinger T
Acta Neuropathol
2014[]; 127
(6
): 897-909
PMID24777482
show ga
Diffuse intrinsic pontine glioma (DIPG), with a median survival of only 9 months,
is the leading cause of pediatric brain cancer mortality. Dearth of tumor tissue
for research has limited progress in this disease until recently. New
experimental models for DIPG research are now emerging. To develop preclinical
models of DIPG, two different methods were adopted: cells obtained at autopsy (1)
were directly xenografted orthotopically into the pons of immunodeficient mice
without an intervening cell culture step or (2) were first cultured in vitro and,
upon successful expansion, injected in vivo. Both strategies resulted in pontine
tumors histopathologically similar to the original human DIPG tumors. However,
following the direct transplantation method all tumors proved to be composed of
murine and not of human cells. This is in contrast to the indirect method that
included initial in vitro culture and resulted in xenografts comprising human
cells. Of note, direct injection of cells obtained postmortem from the pons and
frontal lobe of human brains not affected by cancer did not give rise to
neoplasms. The murine pontine tumors exhibited an immunophenotype similar to
human DIPG, but were also positive for microglia/macrophage markers, such as
CD45, CD68 and CD11b. Serial orthotopic injection of these murine cells results
in lethal tumors in recipient mice. Direct injection of human DIPG cells in vivo
can give rise to malignant murine tumors. This represents an important caveat for
xenotransplantation models of DIPG. In contrast, an initial in vitro culture step
can allow establishment of human orthotopic xenografts. The mechanism underlying
this phenomenon observed with direct xenotransplantation remains an open
question.
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