Scientists at Huntsman Cancer Institute at the University of Utah reported yesterday in Developmental Cell that sustained Ptf1a expression could prevent and reverse tumor initiation in the pancreas.
Ptf1a is a protein used by pancreas cells to override genetic changes and remain "differentiated" or healthy. According to senior author Charles Murtaugh, Ph.D., "Differentiated cells are non-dividing and well-behaved. Ptf1a maintains this good behavior in differentiated cells of the pancreas."
The researchers primarily worked with mouse models. They introduced cancer-causing mutations into normal cells. When pancreatic cancer occurs, Ptf1a is always shut down. Researchers were able to prevent that and found keeping Ptf1a on was enough to completely block pancreatic cancer cells from forming. They also found early-stage cancer cells reverted back to normal pancreas cells when Ptf1a was turned back on. Ptf1a also blocked the growth of late-stage cancer cells.
Then the researchers took their experiment into human pancreatic cancer cell lines. They found turning on Ptf1a blocked the growth of cancer in about half of these cell lines. Murtaugh said this result was surprising. " Ptf1a made pancreas cancer cells behave normally, and this property correlated with its ability to activate differentiation."
Lead author Nathan M. Krah says the strength of this research is showing pancreatic differentiation is a powerful way to prevent and reverse cancer initiation in a variety of models and circumstances. "We varied conditions and timing of re-differentiations and always obtained the same result—expression of Ptf1a was sufficient to stop cancer initiation and progression."