Evaluation of a transplantable mouse brain tumour: a model for the study of human glioma

Abstract

Three cell lines — VMDk P560, P540 and P497 — derived from a transplantable spontaneous murine astrocytoma have been characterised in vitro and in vivo. The cell lines expressed astrocytic features, including the presence of glial fibrillary acidic protein (GFAP) and glutamine synthetase (GS) and showed an enhanced arborisation of cell processes on exposure to dibutyryl adenosine 3′5′ cyclic monophosphate (dbcAMP). Transmission and scanning electron microscopy revealed morphological differences in their degree of cellular differentiation. In vitro growth properties of the cells correlated well with the extent of differentiation.

Cells were injected intracerebrally and subcutaneously into syngeneic mice. The best differentiated cell line — P560 — failed to produce gliomas while transplantation of the least well differentiated line — P497 — resulted in a 100% tumour incidence at both subcutaneous and intracerebral sites. Intracerebral inoculation of P540 gave rise to a 5% tumour incidence. In order to characterise their cellular composition and development tumours were examined by light and electron microscopy and immunocytochemistry.

Although tumours produced by P497 have a consistent, short latency, they have two disadvantages: intracerebral growth tends to be by expansion rather than invasion and the number of brain tumours with accompanying extracranial components is high. P540, although showing limited tumorigenicity in vivo, produces invasive astrocytomas and therefore approximates best the requirements of an ideal transplantable brain tumour model.