Stuart S. Martin, Ph.D., assistant professor of Physiology in the University of Maryland School of Medicine and a researcher in the Hormone Responsive Cancers Program at the University of Maryland Marlene and Stewart Greenebaum Cancer Center, has received a Department of Defense Breast Cancer Concept Award to study tumor evolution in breast cancer. The one-year, $110,000 award was among the only 7% of applications funded out of 1,285 submssions.
Does Apoptotic Resistance Provide an Opportunity for Independent Tumor Evolution?
Breast tumor cells may spread throughout the body very early, but fail to grow into active tumors until much later. Nearly 90% of human solid tumors arise as carcinomas from epithelial cells. Normally, when epithelial cells detach from their home organ, they rapidly commit suicide, which is thought to limit their metastatic spread. We have shown that when mammary epithelial cells resist this suicide, they can survive the challenges of spreading through the bloodstream. However, these cells will not actively grow into tumors and may remain dormant for extended periods.
Large cancer cells often get trapped in the narrow capillaries of the lung. If breast tumor cells can survive long-term in the lung, then environmental toxins, such as cigarette smoke or radon, could activate these dormant cells. These cells would evolve independently from the primary tumor, sustaining different genetic mutations, and may explain why some patients present with metastatic disease without a clear primary tumor, and why metastatic tumors often respond differently to therapy.
We will trap mammary epithelial cells which resist cell death in the lungs of mice by intravenous injection. By testing how long these cells survive and whether they can be activated to grow at a later time, we will establish whether resistance to cell death allows such independent tumor evolution, and should be considered during the development of therapies for metastatic breast cancer.