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.