Nine out of ten Canadians killed by cancer, die because their tumour has spread to other parts of their body. The spread of cancer (metastasis) occurs when tumour cells escape the original primary tumour and colonize other organs to form life-threatening tumour metastases. We are beginning to realize that normal cells can help metastatic tumour cells to survive and grow into tumour metastases. If we can understand how normal cells encourage the development of tumour metastases, we will be able to design more effective therapies to treat metastatic cancer. We have discovered that poorly oxygenated (hypoxic) cells in breast tumours produce proteins that cause normal cells to be released from the bone marrow, enter the bloodstream, and build-up in tissues such as the lung and liver. These bone marrow cells create nests for metastasizing tumour cells to inhabit, providing fertile regions of tissue that allow tumour cells to grow into large tumour metastases. We predict that preventing bone marrow cells from building up in tissues will disrupt the growth of tumour metastases. My research team will use animal models of breast cancer to study the proteins produced by hypoxic tumour cells that cause bone marrow cells to build-up in the lungs and liver. We will also study how surgical primary tumour removal, chemotherapy treatment, and the use of new drugs that target hypoxic tumour cells affect the number and function of bone marrow cells in tissues. We predict that bone marrow cells remain in tissues after therapy and can promote the later development of metastatic tumour recurrences. To improve the health of Canadians we need to better understand metastasis, the leading cause of cancer-related deaths. This proposal will provide important insights into how hypoxic breast tumour cells corrupt normal cells to increase the spread of breast cancer, and will provide a strong basis for the design of new and effective treatments for patients with metastatic cancer.