Cell migration is required during development of the nervous system. The regulatory mechanisms for this process, however, are poorly elucidated. We show here that expression of or exposure to the
neural cell adhesion molecule (
NCAM) strongly affected the motile behaviour of
glioma cells independently of homophilic
NCAM interactions. Expression of the transmembrane 140 kDa
isoform of
NCAM (NCAM-140) caused a significant reduction in cellular motility, probably through interference with factors regulating cellular attachment, as NCAM-140-expressing cells exhibited a decreased attachment to a
fibronectin substratum compared with
NCAM-negative cells. Ectopic expression of the cytoplasmic part of NCAM-140 also inhibited cell motility, presumably via the non-
receptor tyrosine kinase p59(fyn) with which NCAM-140 interacts. Furthermore, we showed that the extracellular part of
NCAM acted as a paracrine inhibitor of
NCAM-negative cell locomotion through a heterophilic interaction with a
cell-surface receptor. As we showed that the two N-terminal
immunoglobulin modules of
NCAM, which are known to bind to
heparin, were responsible for this inhibition, we presume that this receptor is a
heparan sulfate proteoglycan. A model for the inhibitory effect of
NCAM is proposed, which involves competition between
NCAM and extracellular components for the binding to membrane-associated
heparan sulfate proteoglycan.