A new mouse study by researchers at Barts Cancer Institute at Queen Mary University of London, reveals new insight into how healthy cells help pancreatic tumors develop, which may pave the way for the development of new drugs for pancreatic cancer.
Their findings are published in Cell Reports in a paper titled, “Disruption of pancreatic stellate cell myofibroblast phenotype promotes pancreatic tumor invasion,” and led by Angus Cameron, PhD, senior lecturer at Barts Cancer Institute.
The researchers discovered that blocking the expression of a protein, called PKN2, changed the behavior of healthy cells around the tumor called fibroblasts. Their findings suggest targeting fibroblasts may change their behavior and affect how pancreatic cancer develops.
When the researchers blocked expression of PKN2 in the healthy cells of a preclinical model of pancreatic cancer, the tumor grew more aggressively.
“Fibroblasts are like the gatekeepers of pancreatic cancer tumors, and our findings suggest that they can have both positive and negative roles to play in cancer progression,” explained Shinelle Menezes, PhD, postdoctoral researcher in Cameron’s laboratory and joint first author of the study said.
“We found that, when activated through PKN2, fibroblasts can actually act as a defense mechanism to limit cancer spread by keeping the cancer cells tightly compacted within the tumor. Blocking PKN2 suppresses the ability of fibroblasts to contain the cancer cells; however, it also means that they may let more immune cells into the tumor. This novel finding could have broad implications for how we target stromal fibroblasts to treat cancer.”
The researchers are now studying the altered profile of immune cells within pancreatic cancer tumors.
“To improve the outcomes for patients, we need to identify new strategies to target cancer cells as well as the normal cells supporting cancer growth, and find ways to help the body’s immune system fight back against cancer,” Cameron explained.
“Our study contributes to the understanding of the biology of the invasive process in pancreatic cancer, and the roles that fibroblasts play. In our future work, we hope to identify effective drugs to target PKN2, which can be used in laboratory models of pancreatic and other cancers. This will allow us to test how targeting this pathway changes the way cancers develop, which is a key step towards clinical application.”