Our researchers have made several fundamental discoveries which involve the role of bone marrow-derived stem and progenitor cells in tumor blood vessel formation and in metastasis (the spread of cancerous cells). Dr. David C. Lyden, an internationally recognized leader in cancer research, and his team were the first to identify two bone marrow-derived cells that both participate in the formation of new blood vessels in the primary tumor that occurs by vasculogenesis, or new blood vessel formation as opposed to angiogenesis, vessels branching from pre-established blood vessels.
Currently, Dr. Lyden and his team are examining the “microenvironment” of what is known as the metastic site - the enzymes, proteins, and growth factors that encourage cancerís spread. They have identified a type of stem/progenitor cell originating in the bone marrow, called vascular endothelial growth factor receptor 1+ (VEGRF1+). These cells are found in extremely small numbers in the bone marrow and usually remain dormant until “awakened” by specific chemicals called “growth factors”. In the case of VEGFR1+ cells, it was observed that growth factors released by primary cancers triggered this awakening. As tumor-exuded growth factors circulated in the bloodstream, VEGFR1+ cells began to cluster together, moving out of the marrow and settling in specific sites in various organs. These sites were found to be the same as those that are eventually occupied by metastatic cancer cells that spread from the primary tumor. Dr. Lyden’s team also discovered that fibronectin - a protein secreted naturally by cells called fibroblasts - acts as a kind of glue, helping VEGFR1+ cells settle in the “pre-metastatic niche.” This partnership of cells and proteins creates the ideal environment for migrating cancer cells, in exactly the location they are seeking depending on their specific cancer type. In addition to helping identify individuals who may need preventive therapies to reduce their chance of metastatic disease, this groundbreaking work may eventually lead to methods of preventing primary cancers from spreading.