Anchorage of cells to "
heparin"--binding domains that are prevalent in extracellular matrix (ECM) components is thought to occur primarily through the
syndecans, a four-member family of transmembrane
heparan sulfate proteoglycans that communicate environmental cues from the ECM to the cytoskeleton and the signaling apparatus of the cell. Known activities of the
syndecans trace to their highly conserved cytoplasmic domains and to their
heparan sulfate chains, which can serve to regulate the signaling of
growth factors and morphogens. However, several emerging studies point to critical roles for the
syndecans' extracellular protein domains in
tumor cell behavior to include cell adhesion and invasion. Although the mechanisms of these activities remain largely unknown, one possibility involves "co-receptor" interactions with
integrins that may regulate
integrin function and the cell adhesion-signaling phenotype. Thus, alterations in
syndecan expression, leading to either overexpression or loss of expression, both of which take place in
tumor cells, may have dramatic effects on
tumor cell invasion.