Models for CNS malignancies

Primary or intrinsic central nervous system (CNS) tumours, which affect the brain, spinal cord, and cranial nerves, are derived from the CNS substance itself, with the majority of them emanating from neuroglial cells or their progenitors. These tumours are, generally, collectively known as gliomas. Although such neoplasms are quite amenable to cell culture and the established cell lines are numerous, the original tumours display a high degree of cellular heterogeneity, while resultant high-passage cultures suffer from homogeneity due to in vitro selection, thereby limiting their value in biological studies. Monolayer cultures have, however, been used extensively for drug chemosensitivity and multidrug resistance studies, as well as for studies of adhesion, motility, and invasiveness. The use of three-dimensional (3D) multicellular tumour spheroids (MCTSs) has gained much support in recent years often in the context of “confrontation” cultures, where a 3D “target” tissue of precultured heart fragment or re-aggregated brain cells is juxtaposed with the tumour spheroid in order to study interaction between neoplastic and non-neoplastic cell populations. Local invasiveness is frequently monitored by such means. Animal models of primary brain tumour suffer from a number of problems related to their biological differences with spontaneous brain tumours in man. Such animal models may be developed either by exposure to ionizing radiation, chemical carcinogens, or oncogenic viruses or by genetic manipulation. Alternatively, tumour cells or tissues may be either syngeneically transplanted into same-species hosts or xenografted, such as when human biopsy tissue is implanted into immunologically deprived host animals. In addition to hosting primary, intrinsic brain and spinal tumours, the CNS plays host to many secondary or metastatic cancers, which originate in different, distant organs and tissues. Indeed, around a quarter of all cancers spread into the CNS, with seeding into the CNS generally bringing with it a poorer prognosis. Animal models of metastasis into the CNS are rare, as are in vitro models. This is probably a reflection of the underinvestment of time and resources in this branch of oncology. The interaction between metastatic cancer cells and the modified blood vascular system of the brain, which incorporates the structural and physiological blood-brain barrier (B-BB), may be considered an interesting area for further investigation as may the direct interaction between metastatic cancer cells and the brain substance, which provides a “fertile soil” for their growth, but seems to provide a barrier to their invasive behaviour and, hence, growth is essentially proliferative in nature.