APPICAN EXPRESSION INDUCES MORPHOLOGICAL-CHANGES IN C6 GLIOMA-CELLS AND PROMOTES ADHESION OF NEURAL CELLS TO THE EXTRACELLULAR-MATRIX

Appicans are secreted or cell-associated brain chondroitin sulfate pro teoglycans produced by glia cells and containing Alzheimer amyloid pre cursor protein (APP) as a core protein. Here, we report that rat C6 gl ioma cells transfected with appican displayed a dramatic change in the ir phenotypic appearance compared with untransfected cells or cells tr ansfected with APP. Appican-transfected cells lost the round appearanc e of the untransfected control C6 cells, acquired a flat morphology, a nd elaborated more processes than control cells. Untransfected, or APP -transfected C6, cells were completely dissociated from their substrat e after 40 min of treatment with cell dissociation solution. Under the same conditions, however, <20% of the appican-transfected C6 cells we re dissociated from their substrate, suggesting that the appican-trans fected glia cells attach more avidly to their substrate than do untran sfected or APP transfected control cells. In contrast, appican-transfe cted fibroblast cells showed no morphological changes and dissociated from their substrate similarly to untransfected fibroblast cells. Extr acellular matrix (ECM) prepared from appican-transfected C6 cell cultu res contained high levels of appican and was a significantly better su bstrate for the attachment of C6 cells than ECM from either untransfec ted or APP-transfected cultures. Furthermore, cell adhesion to ECM was independent of the level of appican expression of the plated cells. E CM from appican-transfected C6 cultures stimulated adhesion of other n eural cells including primary astrocytes, Neuro2a neuroblastoma, and P C12 pheochromocytoma, but not fibroblast cells. Conditioned media from appican-transfected C6 cultures failed to promote cell adhesion. Toge ther, these data suggest that secreted appican incorporates into ECM a nd promotes adhesion of neural cells. Furthermore, our data suggest th at the chondroitin sulfate chain engenders APP with novel biological f unctions.