Syndecan-1 modulates IL-6- and beta-integrin- dependent functions in breast cancer cell adhesion and migration

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. Here, we evaluate the potential role of Syndecan-1 in modulating matrix-dependent breast cancer cell migration in the presence of Interleukin-6 in vitro. MDA-MB-231 breast cancer cells were transiently transfected with Syndecan-1 siRNA or control reagents, followed by stimulation with Interleukin-6. Cellular responses were monitored by adhesion- and migration 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, while RGD peptides inhibited both adhesion and migration. Interleukin-6-induced activation of focal adhesion kinase and reduction of constitutive NF-kB signaling were decreased in Syndecan-1-deficient cells. We conclude that loss of Syndecan-1 induces cell adhesion and migration through a focal adhesion kinase-integrin signaling pathway which is modulated by the inflammatory microenvironment.