Activation of tissue plasminogen activator by metastasis-inducing S100P protein.

摘要: S100P protein in human breast cancer cells is associated with reduced patient survival and, a model system of metastasis, it confers metastatic phenotype upon benign mammary tumour cells. possesses C-terminal lysine residue. Using multiwell vitro assay, now shown for the first time to exhibit strong, lysine-dependent activation tissue plasminogen activator (tPA), but not urokinase-catalysed activation. The presence 10 μM calcium ions stimulates tPA 2-fold an S100P-dependent manner. physically interacts both and , urokinase. Cells constitutively expressing detectable on cell surface, S100P-containing show enhanced compared S100P-negative control shows enhancement invasion. An antibody, when added culture medium, rate invasion wild-type S100P-expressing cells, mutant proteins lacking lysine, suggesting that functions outside cell. protease inhibitors, aprotinin or α-2-antiplasmin, nor lysine. It proposed via contributes by thus potentially its metastasis-promoting activity.