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Syndecan‐1 modulates β‐integrin‐dependent and interleukin‐6‐dependent functions in breast cancer cell adhesion, migration, and resistance to irradiation
Author(s) -
Hassan Hebatallah,
Greve Burkhard,
Pavao Mauro S. G.,
Kiesel Ludwig,
Ibrahim Sherif A.,
Götte Martin
Publication year - 2013
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.12111
Subject(s) - syndecan 1 , focal adhesion , fibronectin , microbiology and biotechnology , cell adhesion , cancer research , integrin , cytokine , biology , extracellular matrix , signal transduction , cell adhesion molecule , chemistry , cell , immunology , biochemistry
Syndecan‐1 is a cell surface heparan sulfate proteoglycan with various biological functions relevant to tumor progression and inflammation, including cell–cell adhesion, cell–matrix interaction, and cytokine signaling driving cell proliferation and motility. Syndecan‐1 is a prognostic factor in breast cancer, and has a predicitive value for neodadjuvant chemotherapy. It is still poorly understood how syndecan‐1 integrates matrix‐dependent and cytokine‐dependent signaling processes in the tumor microenvironment. Here, we evaluated the potential role of syndecan‐1 in modulating matrix‐dependent breast cancer cell migration in the presence of interleukin‐6, and its potential involvement in resistance to irradiation in vitro . MDA ‐ MB ‐231 breast cancer cells were transiently transfected with syndecan‐1 small interfering RNA or control reagents, and this was followed by stimulation with interleukin‐6 or irradiation. Cellular responses were monitored by adhesion, migration and colony formation assays, as well as analysis of cell signaling. Syndecan‐1 depletion increased cell adhesion to fibronectin. Increased migration on fibronectin was significantly suppressed by interleukin‐6, and GRGDSP peptides inhibited both adhesion and migration. Interleukin‐6‐induced activation of focal adhesion kinase and reduction of constitutive nuclear factor kappaB signaling were decreased in syndecan‐1‐deficient cells. Focal adhesion kinase hyperactivation in syndecan‐1‐depleted cells was associated with dramatically reduced radiation sensitivity. We conclude that loss of syndecan‐1 leads to enhanced activation of β 1 ‐integrins and focal adhesion kinase, thus increasing breast cancer cell adhesion, migration, and resistance to irradiation. Syndecan‐1 deficiency also attenuates the modulatory effect of the inflammatory microenvironment constituent interleukin‐6 on cancer cell migration.