Integrin ß3 and its ligand regulate the expression of uPA through p38 MAPK in breast cancer.

Interplay between integrins and extracellular matrix is suggested to play an important role in malignant progression and tumor differentiation. The aim of the study was to determine the combined expression of integrin ß3 and tenascin-c (TN-c) in breast cancer and examine whether integrin ß3 and TN-c can activate urokinase-type plasminogen activator (uPA) through p38 mitogen-activated protein kinase (p38 MAPK). We detected the expression of integrin ß3, TN-c, p-p38, and uPA in 80 cases of breast invasive ductal carcinoma by immunohistochemistry. In addition, we blocked integrin ß3 and TN-c in the MDA-MB-231 breast cancer cells and detected the expression of p-p38 and uPA by Western blot. Integrin ß3, TN-c, p-p38, and uPA showed high levels of expression in breast invasive ductal carcinoma. The expression of integrin ß3, TN-c, and uPA was correlated with lymph node metastasis and TNM stage in breast cancer. Furthermore, correlations were noted between any two of the three proteins. The expression of p-p38 and uPA decreased in MDA-MB-231 cells after the addition of integrin ß3 antibody and TN-c antibody. The expression of uPA decreased after addition of SB203580. Our results demonstrate that inhibition of the expression of integrin ß3 and TN-c could decrease the expression of uPA through p38 MAPK in breast cancer, suggesting that the interaction between integrin ß3 and TN-c serves an important role in breast cancer.