Identification of Serine Proteinases Involved in Breast Cancer Progression

PUBLIC ABSTRACT

Proteinases are enzymes that digest other proteins. While they fulfill many important and essential functions, the increased activity of certain proteinases is required for the invasion of cancers into surrounding tissues and for metastatic dissemination. Drugs that specifically target these tumorigenic proteinases present a promising approach to cancer therapy. Using a physiologically relevant, three-dimensional culture model for human breast cancer, we have discovered that treatment with an inhibitor of a class of proteinases can block the uncontrolled, disorganized growth displayed by malignant cells, actually "normalizing" the tumor cells. We hypothesize that this "normalizing" effect is caused by inhibition of a specific (but as yet unidentified) tumorigenic proteinase, and that once identified, this proteinase may represent a novel and promising target for breast cancer treatment. We propose to identify the proteinase(s) for which specific inhibition in our breast cancer model leads to the apparent suppression of malignancy. Identification of the proteinase(s) involved will lay the groundwork for future development of new molecularly targeted agents for treatment of breast cancer.