SEP 27, 2021

Inflammation Promotes Pancreatic Cancer Progression

WRITTEN BY: Katie Kokolus

Inflammation occurs when the immune response, including immune cells and mediators they produce, protect you from dangerous pathogens like viruses and bacteria.  In addition to attacking foreign invaders, many conditions, such as arthritis, asthma, and diabetes, are linked to inflammation.

The association between cancer and inflammation was documented as early as 1863 when Rudolf Virchow found white blood cells, also known as leukocytes, infiltrating neoplastic tissue.  Today, while the relationship between cancer and inflammation is more fully understood, researchers are actively exploring specific biological mechanisms involved.  

A study recently published in Science clarifies some of the mechanisms underlying inflammation-associated pancreatic cancer.  The research team investigated the impact of inflammation on the cells lining the pancreas, known as pancreatic epithelial cells.

Researchers induced inflammation in a mouse model of pancreatic ductal adenocarcinoma (PDAC).  Inflammatory cells infiltrated and proliferated in the pancreatic tissue following induction of inflammation.  Without further intervention, the inflammation began to resolve within a week and the immune cell profile returned to pre-induction levels in less than a month.   

The study also explored the effect of inflammation on KRAS-driven pancreatic cancer, which is representative of 95% of PDACs. Following activation of KRAS in the murine system, mice exposed to inflammation experienced accelerated tumor growth and succumbed to disease, while control mice were largely unaffected.  

Surprisingly, even when KRAS was activated three months following the inflammatory event, the tumors in mice exposed to inflammation progressed significantly faster than in control mice.  These findings suggest that inflammation imposes long-lasting alterations in pancreatic epithelial cells.  Further, when in the presence of mutant KRAS, these reprogrammed cells promote cancer progression.

Following inflammation, extensive molecular analysis of pancreatic epithelial cells demonstrated considerable modifications in gene expression.  Many of the genes activated post-inflammation, including those associated with cell survival and proliferation, have well-established roles in tumor development. The authors describe the genetic alterations that were still evident long after the inflammation resolved as epithelial memory.   

The study solidifies specific mechanisms involved in inflammation-associated pancreatic cancer.  As pancreatic cancer has one of the lowest five-year survival rates among all cancer sites, these findings are valuable to researchers as they continue to seek life-saving treatments for pancreatic cancer.

 

Sources: Inflammation1863leukocytesneoplasticScience95%five year survival