One heparan sulfate proteoglycan (HSPG) coreceptor is not like another. On page 729, Ding et al. show how two HSPGs, both capable of acting as growth factor coreceptors, have distinct functions on cancer cells. Glypican-1 acts as a long-term growth factor coreceptor, whereas syndecan-1 is shed and helps spread a metasis-promoting proteinase.
Upon stimulation with fibroblast growth factor-2 (FGF2), the initial responses of pancreatic cancer cells could be facilitated either by glypican-1 or syndecan-1. Yet the cells rapidly became dependent on glypican-1.
The researchers found that the extracellular domain of syndecan-1 was proteolytically clipped off the membrane in response to FGF2. No evidence of glypican-1 cleavage was found. Noncleavable syndecan-1 blocked syndecan-1 shedding and kept cells responsive to FGF2, even in the absence of glypican-1.
Stimulation by FGF2 induced activation of matrix metalloproteinase-7 (MMP7), which was responsible for the shedding of the extracellular domain...
