Role of different cathepsins in the invasion of MDA‐MB‐231 human breast cancer cells (1148.6)

Abstract

For the progression of tumor towards the malignancy such as invasion and metastasis, proteolytic activity is required for the degradation of the basement membrane and extracellular matrix. Matrix metalloproteinases (MMPs) were reported to play a major role in the proteolytic action. In addition to MMPs, cathepsins have emerged as an important molecular target for the management of cancer. They play a vital role in extracellular matrix degradation which accelerates the process of cancer cell invasion. Although cathepsin D (catD), a aspartyl protease, is overexpressed and secreted by cells of various tumor types including breast carcinomas, we found that cysteine proteases (catB, catK, catL and catS) rather than the aspartyl proteases participates in the invasion when they were blocked by siRNA transfection and specific inhibitors. In addition, combination of catB and catS inhibitor showed an additive effect on the inhibition of in vitro matrigel invasion. The result was correlated when both catB and catS were silenced by siRNA. Our data suggest that among the cysteine proteases, catB and catS are the key target enzymes for the invasion of highly metastatic breast cancer cells (MDA‐MB‐231). CatS has been suggested as a target for management of autoimmunity‐related disease such as arthritis without adverse effect (Nakagawa et al., 1999). Taken together, our results implicate that catS may be a good candidate target for new drug development for the management of human breast cancer metastasis.