The tumor microenvironment plays a major role in promoting the growth and invasion of cancer cells. In pancreatic ductal adenocarcinoma—the third leading cause of cancer death in the United States—a dense layer of connective tissue known as fibrotic stroma surrounds the developing tumor. Cancer-associated fibroblasts (CAFs) are a major component of the stroma and influence whether the cancer will invade, metastasize or become resistant to chemotherapy. Discovering the mechanisms leading to CAF development in pancreatic ductal adenocarcinoma could lead to desperately needed new therapies.

In a paper published online on October 30 in eLife, researchers from Einstein and other institutions report that lactate (lactic acid) plays a role in CAF formation in pancreatic cancer. Lactate secreted by pancreatic cancer cells epigenetically reprograms mesenchymal stem cells to form CAF cells that in turn promote the progression of pancreatic tumors. The findings suggest that lactate inhibitors may be useful in treating pancreatic cancer.

Co-corresponding author Amit Verma, M.B.B.S., is professor of medicine and of developmental and molecular biology at Einstein and attending physician in oncology at Montefiore Einstein Center for Cancer Care. First author Tushar Bhagat, Ph.D., is research assistant professor of medicine at Einstein. Anirban Maitra, M.B.B.S., of MD Anderson Cancer Center and Deepak Nagrath, Ph.D., of the University of Michigan were also corresponding authors.