Significance of S100A10 (p11) in breast cancer tumor progression

Breast cancer is the second leading cause of cancer death in Canadian women. The high incidence of deaths linked to this cancer is due to spreading (metastasis) of the cancer to organs such as lungs and bones. Cancer cell spreading is assisted by a protein called plasmin which chews other proteins surrounding the tumor cells thereby making the way for the cancer cells to move from the tumor site to distant organs. Plasmin is produced from a blood protein called, plasminogen, by the action of proteins located on the surface of the cancer cells. One such protein, S100A10 (p11), binds plasminogen on the cell surface and speeds up plasmin formation. In our initial studies, we observed that breast tumors and metastasis to the lung are dramatically reduced in mice engineered not to make p11 (p11- null). Moreover, we have shown, by analyzing breast cancer patient tumor samples, that patients with low p11 levels in their breast tissue have a better rate of survival than patients with high p11 levels. In the current project, we will investigate how p11 affects tumor growth and metastasis in breast cancer using a well-established breast cancer mouse model that is known to mimic human breast cancer, the PyMT mouse model. We will determine if the plasmin generated by p11 is important for the ability of the cancer cells to develop tumors, leave the tumor site and/or grow in other tissues. We will determine if the reduction in tumor growth seen when cancer cells cannot produce p11 is due to decreased cancer cell growth or increased cancer cell death. We will also determine if p11 produced by the other cells in the tumor that support cancer cell development and growth are important or necessary for tumor growth and metastasis. Identifying the mechanisms by which p11 contributes to tumor growth and metastasis will facilitate the development of new therapies to block tumor growth and metastasis by specifically targeting p11.