Clipping coreceptors
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《细胞学杂志》
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 of syndecan-1. Because MMP7 is normally docked on cell surfaces by binding to HSPGs, its activation by FGF2 induced its own release, in association with shed syndecan-1 ectodomains.
The team thinks that growth factor–induced release of MMP7–syndecan-1 complexes from tumor cells enhances the ability of MMPs to diffuse out of tumors and degrade surrounding extracellular matrix, an early step in metastasis. MMP7 is know to facilitate metastasis, and recent evidence indicates that forcing tumor cells to shed syndecan-1 constitutively also makes them more aggressive in vivo.(One heparan sulfate proteoglycan (HSPG) )
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 of syndecan-1. Because MMP7 is normally docked on cell surfaces by binding to HSPGs, its activation by FGF2 induced its own release, in association with shed syndecan-1 ectodomains.
The team thinks that growth factor–induced release of MMP7–syndecan-1 complexes from tumor cells enhances the ability of MMPs to diffuse out of tumors and degrade surrounding extracellular matrix, an early step in metastasis. MMP7 is know to facilitate metastasis, and recent evidence indicates that forcing tumor cells to shed syndecan-1 constitutively also makes them more aggressive in vivo.(One heparan sulfate proteoglycan (HSPG) )