Syndecan-2 Regulates the Invasive Phenotype of Human Breast Carcinoma Cells

Syndecans are heparan sulphate proteoglycans that have prominent roles in integrin‐dependent cell adhesion. However, their function in tumorigenesis remains elusive. We have demonstrated that depletion of syndecan‐2 or syndecan‐4 in MDA‐MB‐231 human breast cancer cells inhibits type I collagen invasion and degradation. Moreover, syndecan‐2 deficiency promotes marked cell spreading and microfilament bundle, focal adhesion and adherens junction formation. Conversely, syndecan‐4 depletion had no effect on cell spreading or actin cytoskeletal organization. The focal adhesions that form after syndecan‐2 depletion were, however, syndecan‐4 dependent. This suggests that in breast carcinoma cells syndecan‐2 may suppress syndecan‐4 function. In addition, exogenous heparin or heparan sulphate also blocked invasion via inhibition of thrombin. This suggests important roles for cell surface heparan sulphate in tumor cell behavior. Taken together, syndecan‐2 appears to support the invasive phenotype of breast carcinoma cells by regulating cell morphology and cytoskeletal organization.