Publication: Standardization of an
orthotopic mouse brain tumor model
following transplantation of CT-2A astrocytoma cells
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Date
2007
Authors
Martínez Murillo, R. ; Martínez, A.
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Publisher
Murcia: F. Hernández
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DOI
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info:eu-repo/semantics/article
Description
Abstract
Animal models of glial-derived neoplasms
are needed to study the biological mechanisms of glioma
tumorigenesis and those that sustain the disease state.
With the aim to develop and characterize a suitable in
vivo experimental mouse model for infiltrating
astrocytoma, with predictable and reproducible growth
patterns that recapitulate human astrocytoma, this study
was undertaken to analyze the long-term course of a
syngeneic orthotopically implanted CT-2A mouse
astrocytoma in C57BL/6J mice. Intracranial injection of
CT-2A cells into caudate-putamen resulted in
development of an aggressive tumor showing typical
features of human glioblastoma multiforme, sharing
close histological, immunohistochemical, proliferative,
and metabolic profiles. To simulate metastatic disease to
the brain, CT-2A cells were injected through the internal
carotid artery. Tumors identical to those obtained by
intracranial injection were obtained. Finally, CT-2A cells
were re-isolated from experimental brain tumors and
transcranially re-injected into the caudate-putamen of
healthy mice. These cells generated new tumors that
were indistinguishable from the initial ones, suggesting
in vivo self-renewal of tumor cells. Small-animal models
are essential for testing novel biological therapies
directed against relevant molecular targets. In a
preliminary study, experimental CT-2A tumors were
chronically treated with the small molecule 77427, a
gastrin-releasing peptide (GRP) blocker compound that
inhibits angiogenesis. Treated animals developed
significantly smaller tumors than controls, suggesting an
antitumor action for 77427 in glioblastomas. We
conclude that the orthotopic CT-2A tumor model, as
described herein, is appropriate to explore the
mechanisms of glioma development and for preclinical
trials of promising drugs.
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