Growth factor-induced shedding of syndecan-1 confers glypican-1 dependence on mitogenic responses of cancer cells

Kan Ding, Martha Lopez-Burks, José Antonio Sánchez-Duran, Murray Korc, Arthur D. Lander

Research output: Contribution to journalArticle

90 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)729-738
Number of pages10
JournalJournal of Cell Biology
Volume171
Issue number4
DOIs
StatePublished - Nov 21 2005
Externally publishedYes

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Glypicans
Syndecan-1
Intercellular Signaling Peptides and Proteins
Fibroblast Growth Factor 2
Heparan Sulfate Proteoglycans
Neoplasms
Matrix Metalloproteinase 7
Syndecans
Pancreatic Neoplasms
Breast Neoplasms

ASJC Scopus subject areas

  • Cell Biology

Cite this

Growth factor-induced shedding of syndecan-1 confers glypican-1 dependence on mitogenic responses of cancer cells. / Ding, Kan; Lopez-Burks, Martha; Sánchez-Duran, José Antonio; Korc, Murray; Lander, Arthur D.

In: Journal of Cell Biology, Vol. 171, No. 4, 21.11.2005, p. 729-738.

Research output: Contribution to journalArticle

Ding, Kan ; Lopez-Burks, Martha ; Sánchez-Duran, José Antonio ; Korc, Murray ; Lander, Arthur D. / Growth factor-induced shedding of syndecan-1 confers glypican-1 dependence on mitogenic responses of cancer cells. In: Journal of Cell Biology. 2005 ; Vol. 171, No. 4. pp. 729-738.
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