Grant: Operating Grant

Human cells have several natural mechanisms of counteracting the development of cancer. One of these mechanisms forces potential cancer cells to stop dividing and rest, but not to regress or disappear. The easiest demonstration of this is skin moles, almost all of which have high levels of proteins that drive the development of cancer. However, skin moles are benign, rarely progressing to malignant melanoma. This is because high levels of cancer causing proteins induce the production of other proteins that cause the potential cancer to stop growing. One of these tumor suppressor proteins, IGFBP7, is the subject of this proposal. It is found at high levels in skin moles, and was recently found to be sufficient to prevent the growth of malignant melanomas. That work suggested to us that IGFBP7 could also act against breast tumors. We have studied IGFBP7 in breast cancer for many years, discovering that it is expressed at high levels in benign breast tumors, and that patients with high levels of IGFBP7 in their tumors have a better prognosis. The overall goal of this new proposal is to determine which tumors will be responsive to IGFBP7 suppression of breast cancer growth and/or spread to other organs. We will use various breast cancer cell lines and our recently developed mouse model of breast cancer metastasis to test the suitability of IGFBP7 as an effective breast tumor therapy. Our team of breast cancer surgeons, breast pathologists, and molecular pathologists is uniquely poised to extend this work to primary human breast cancers.