Cell surface heparan sulfate (HS) proteoglycans are carbohydrate-rich regulators 
of cell migratory, mitogenic, secretory, and inflammatory activity that bind and 
present soluble heparin-binding growth factors (e.g., fibroblast growth factor, 
Wnt, Hh, transforming growth factor beta, amphiregulin, and hepatocyte growth 
factor) to their respective signaling receptors. We demonstrate that the 
deglycanated core protein of syndecan-1 (SDC1) and not HS chains nor SDC2 or -4, 
appears to target the epithelial selective prosecretory mitogen lacritin. An 
important and novel step in this mechanism is that binding necessitates prior 
partial or complete removal of HS chains by endogenous heparanase. This limits 
lacritin activity to sites where heparanase appears to predominate, such as 
sites of exocrine cell migration, secretion, renewal, and inflammation. Binding 
is mutually specified by lacritin's C-terminal mitogenic domain and SDC1's N 
terminus. Heparanase modification of the latter transforms a widely expressed HS 
proteoglycan into a highly selective surface-binding protein. This novel example 
of cell specification through extracellular modification of an HS proteoglycan 
has broad implications in development, homeostasis, and disease.