The Journal of Cell Biology
Geisel School of Medicine
The cell surface heparan sulfate proteoglycan (HSPG) glypican-1 is up-regulated by pancreatic and breast cancer cells, and its removal renders such cells insensitive to many growth factors. We sought to explain why the cell surface HSPG syndecan-1, which is also up-regulated by these cells and is a known growth factor coreceptor, does not compensate for glypican-1 loss. We show that the initial responses of these cells to the growth factor FGF2 are not glypican dependent, but they become so over time as FGF2 induces shedding of syndecan-1. Manipulations that retain syndecan-1 on the cell surface make long-term FGF2 responses glypican independent, whereas those that trigger syndecan-1 shedding make initial FGF2 responses glypican dependent. We further show that syndecan-1 shedding is mediated by matrix metalloproteinase-7 (MMP7), which, being anchored to cells by HSPGs, also causes its own release in a complex with syndecan-1 ectodomains. These results support a specific role for shed syndecan-1 or MMP7-syndecan-1 complexes in tumor progression and add to accumulating evidence that syndecans and glypicans have nonequivalent functions in vivo.
Ding K, Lopez-Burks M, Sánchez-Duran JA, Korc M, Lander AD. Growth factor-induced shedding of syndecan-1 confers glypican-1 dependence on mitogenic responses of cancer cells. J Cell Biol. 2005 Nov 21;171(4):729-38. doi: 10.1083/jcb.200508010. Epub 2005 Nov 14. PMID: 16286510; PMCID: PMC2171561.
Dartmouth Digital Commons Citation
Ding, Kan; Lopez-Burks, Martha; Sánchez-Duran, José A.; Korc, Murray; and Lander, Arthur D., "Growth Factor–Induced Shedding of Syndecan-1 Confers Glypican-1 Dependence on Mitogenic Responses of Cancer Cells" (2005). Dartmouth Scholarship. 1450.