Pancreatic tumor promotion by neighboring cell death

Pancreatic tumor promotion by neighboring cell death

The most aggressive form of pancreatic cancer - often described as one of the hardest malignancies to diagnose and treat -- thrives in the presence of neighboring tumor cells undergoing a particular form of "orchestrated cell death." This is according to a major study published in the journal Nature.

The study results revolve around carefully regulated cell dell death mechanisms that, by killing defective cells or those infected by viruses, are often important cellular defense mechanisms. By studying a mouse model of pancreatic ductal adenocarcinoma (PDAC), researchers from NYU Langone Medical Center found that the form of orchestrated cell death -- called necroptosis -- in fact induced the production of a small protein CXCL1 to drive the growth of PDAC tumor cells.

CXCL1 is known to attract specialized immunosuppressive cells, tumor-associated macrophages, which reduce the ability of the human immune system to recognize and destroy cancer cells. Furthermore, the researchers say that similar events appear to occur in human PDAC.

The team went on to discover that necroptosis-induced CXCL1 alone was not enough to account for the tumor-protective environment created around the tumor cells. Dying tumor cells also release another protein, SAP130, that binds to a receptor called named Mincle, on the cell membranes of inflammatory immune cells located within the tumor environment. Activation of Mincle was found to accelerate tumor formation in mice.

Importantly, the researchers say, this study suggests that necroptosis and Mincle signaling could represent novel targets for potential anti-cancer drug development. Inhibiting these pathways could reverse the immunosuppressive environment created by tumor-associated macrophages and enable another type of immune cell, cancer-killing T lymphocytes, to attack the tumor.