GLIOMA CELL-ADHESION AND MIGRATION ON HUMAN BRAIN SECTIONS

Within the brain, dissemination of glioma cells follows myelinated fib er tracts and extracellular matrix containing structures such as the b asement membranes of blood vessels. These patterns represent the two m ajor routes of invasion frequently observed in clinical disease. Previ ously, we have characterized the substrates for preferential glioma ad hesion and migration on purified ECM protein. In this study sections o f human brain from different anatomical regions were used as adhesive substrates and also characterized for the presence and distribution of matrix proteins. Adhesion of marker gene transfected glioma cell susp ensions to different regions and anatomical structures of human brain was quantified using a computer assisted image analysis system Monoclo nal antibodies against different adhesion molecules were used to inhib it glioma cell attachment to specific anatomical structures. In additi on, glioma cell aggregates were allowed to adhere to brain sections an d single cells were observed to migrate out of these aggregates. scann ing electron microscopy was used to morphologically study the preferre d routes of glioma dissemination on brain sections. In brain sections different kinetics of cell adhesion to distinct structures were observ ed Within 15 minutes cells adhered and spread on blood vessels and ara chnoid tissue containing sections. Choroid plexus and the ventricular wall were also adhesive structures. Adhesion to cortex required I hour , while adhesion and spreading on myelinated fiber tracts was retarded and required several hours of incubation. The predominant matrix prot eins in small vessels were found to be laminin, collagen type IV, and fibronectin. Choroid plexus and the ependyma showed a similar composit ion of matric: proteins. Arachnoid fibers contained different types of collagens, predominately type I and III, whereas the only matric: pro tein identified in the subependyma was fibronectin. Antibodies to the alpha(2), alpha(3) and beta(1) integrin subunits completely blocked ad hesion to arachnoid tissue, anti-NCAM inhibited attachment to cortex A dhesion to blood vessels in brain sections could only be inhibited to 50% by anti-integrin beta 1. Antibodies to the a(v) containing integri n alpha(v)beta(3) also blocked 50% of adhesion to vessels. Our finding s indicate that adhesion of glioma cells to brain sections most rapidl y takes place on ECM protein containing regions, especially blood vess els which may serve as guiding structures for glioma dissemination.