THE ROLE OF THE EXTRACELLULAR-MATRIX IN NEOPLASTIC GLIAL INVASION OF THE NERVOUS-SYSTEM

Intrinsic tumours of the central nervous system (CNS) are generally de rived from the glial cells: the astrocytes, oligodendrocytes and epend ymal cells. Although such tumours rarely metastasize to distant organs , they show a marked propensity for local invasion of the surrounding nervous tissue. Sub-populations of neoplastic glia may migrate several millimetres away from main tumour mass into the contiguous CNS parenc hyma, resulting in poor demarcation of the tumour. These migratory, so -called ''guerrilla'' cells give rise to recurrent tumours following s urgical debulking and adjuvant radio- and chemo-therapeutic interventi on. As in other organs, tumour cell invasion is, in part, facilitated by interaction with the extracellular matrix (ECM); however, apart fro m the vascular basal lamina and the glia limitans externa, the CNS lac ks a well-defined ECM. Invading neoplastic cells must, therefore, prov ide their own ECM, a process which may be stimulated by such agents as gangliosides or growth factors. Glioma cell-derived laminin and hyalu ronic acid may provide the most important substrates for invasion, cel l adhesion to these substrates being achieved largely through integrin receptors (the function of which may be determined by interaction wit h cell surface gangliosides) and CD44, respectively. Modulation of the se ECM components is facilitated by a variety of proteinases including the matrix metalloproteinases and hyaluronidase, the activity of whic h is also thought to stimulate angiogenesis. Interference with the mec hanisms which promote glioma cell adhesive properties may provide suit able targets for novel anti-invasive therapies. These might include EC M components, growth factors, gangliosides, integrin receptors and pro teases and their inhibitors.