Xenograft Transplantation of Human Malignant Astrocytoma Cells Into Immunodeficient Rats: An Experimental Model of Glioblastoma

Abstract

INTRODUCTION:Astrocytic gliomas are the most common intracranial central nervous system neoplasias, accounting for about 60% of all primary central nervous system tumors. Despite advances in the treatment of gliomas, no effective therapeutic approach is yet available; hence, the search for a more realistic model to generate more effective therapies is essential.OBJECTIVE:To develop an experimental malignant astrocytoma model with the characteristics of the human tumor.METHOD:Primary cells from subcutaneous xenograft tumors produced with malignant astrocytoma U87MG cells were inoculated intracerebrally by stereotaxis into immunosuppressed (athymic) Rowett rats.RESULTS:All four injected animals developed non-infiltrative tumors, although other glioblastoma characteristics, such as necrosis, pseudopalisading cells and intense mitotic activity, were observed.CONCLUSION:A malignant astrocytoma intracerebral xenograft model with poorly invasive behavior was achieved in athymic Rowett rats. Tumor invasiveness in an experimental animal model may depend on a combination of several factors, including the cell line used to induce tumor formation, the rat strains and the status of the animal’s immune system.

Changes in the expression of proteins associated with aerobic glycolysis and cell migration are involved in tumorigenic ability of two glioma cell lines

“…The major difference between these human glioblastoma cell lines, U87MG and T98G, is the tumorigenic potential of U87MG cells in nude mice [6,7]. In fact, our in vitro assays showed a higher basal proliferation rate and a higher migration rate of U87MG cells than T98G cells, as reported by others [12-14].…”

“…U87MG is hypo diploid [4] while T98G is a hyperpentaploid cell line [5], a fact that indicates marked changes in their genomes. Moreover, these two cell lines present another major difference: while U87MG cells carry wild-type p53 and are known to be tumorigenic in nude mice [6], T98G cells, harboring the mutant p53, are not tumorigenic. Consequently, p53 mutation alone is inferred not to be sufficient to induce tumorigenesis in nude mice [7].…”

Epidermal Growth Factor Receptor Extracellular Domain Mutations in Glioblastoma Present Opportunities for Clinical Imaging and Therapeutic Development

“…While imaging characteristics can suggest underlying biological processes, verification using animal studies is more conclusive. U87 often displays bulky tumors with little presentation of invasion in orthotopic implantations (Miura et al, 2010). The invasive picture presented by the EGFR A289V mutation represents a significant alteration to both the baseline of U87 and U87-expressing WT EGFR.…”

Correlation of MGMT promoter methylation status with gene and protein expression levels in glioblastoma

“…Glioblastomas (GBMs, World Health Organization Grade IV) are the most frequent and malignant of these gliomas, with tumorigenicity demonstrated even in xenograft models 2. The median survival of GBM patients rarely exceeds 12 months 3,4.…”

“… 1 Glioblastomas (GBMs, World Health Organization Grade IV) are the most frequent and malignant of these gliomas, with tumorigenicity demonstrated even in xenograft models. 2 The median survival of GBM patients rarely exceeds 12 months. 3 , 4 GBMs are divided into two subgroups: primary GBMs that emerge de novo and secondary GBMs that are formed from lower-grade astrocytomas.…”