TUMOR-CELL MIGRATION IN THE CENTRAL-NERVOUS-SYSTEM

Intrinsic tumours of the central nervous system (CNS) are set apart from solid, non-neural primary neoplasms in that, although they seldom metastasize to distant organs, they are generally characterised by a diffuse local invasive pattern. Indeed, it is this important biological characteristic which precludes successful therapeutic intervention in the majority of brain and spinal cord neoplasms. While tumours metastasising to the brain are generally well-circumscribed lesions, sub-populations of neoplastic cells from intrinsic, neuroectodermal tumours may migrate several millimetres away from the brain/tumour interface, resulting in a poor demarcation of the neoplasm. These migratory cells give rise to recurrent tumours following surgical and adjuvant chemo- and radio-therapeutic intervention. The mechanisms which facilitate such migration of neoplastic neural cells into the contiguous normal nervous tissue are poorly documented. However, migration in this context is likely to be a complex multifaceted phenomenon involving cell/cell and cell/extracellular matrix (ECM) adhesion, locomotion, angiogenesis and enzymic degradation of the ECM. In particular, cell adhesion molecules, gangliosides, paracrine and autocrine growth and motility factors and matrix metalloproteinases (MMPs) and their inhibitors probably all play important and inter-dependent roles in the migration of neoplastic neural cells.