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- Title
Growth factor-induced shedding of syndecan-1 confers glypican-1 dependence on mitogenic responses of cancer cells.
- Authors
Ding, Kan; Lopez-Burks, Martha; Sánchez-Duran, José Antonio; Korc, Murray; Lander, Arthur D
- Abstract
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.
- Publication
The Journal of cell biology, 2005, Vol 171, Issue 4, p729
- ISSN
0021-9525
- Publication type
Journal Article
- DOI
10.1083/jcb.200508010