Fountain of youth of pancreatic cancer cells: the extracellular matrix

The microenvironment of tumors varies between cancer types, and its complex role in tumor propagation contributes to its importance in the field of tumor biology. Tumors with a dense microenvironment express aggressive characteristics that directly impact patient clinical outcomes. In pancreatic ductal adenocarcinoma (PDAC), tumor cells are surrounded by various cellular and acellular components including activated fibroblasts, immune cells, neurons, collagens, fibronectin, and hyaluronan, creating a fibrotic shield that impedes chemotherapeutics delivery to tumor cells 1 , 2 , 3 . Accordingly, Whatcott et al. have shown a negative correlation between PDAC-patient median survival and the collagen or hyaluronic acid enrichment of the primary tumor 4 . At the site of PDAC this fibrosis, or desmoplasia, often creates zones of low oxygen and nutrients resulting from poor vascularization 5 . Given these microenvironmental constraints and the resulting metabolic pressure, pancreatic tumor cells adapt their metabolism to benefit from available nutrient resources in order to survive and proliferate. This metabolic reprogramming leads to the emergence of aggressive tumor cells and invasive tumors, which are able to disseminate to distal organs including the liver and lung 6 .