Scientists have learned that pancreatic cancer can form in two different ways, solving long-standing questions. They developed an imaging tool that allowed them to see the development of cancer in 3D. It will enable researchers to learn more about tissues harvested from cancer patients and may help lead to improvements in treatment. The work has been reported in Nature.
"To investigate the origins of pancreatic cancer, we spent six years developing a new method to analyze cancer biopsies in three dimensions," said the co-lead author of the study Dr. Hendrik Messal of the Francis Crick Institute.
The pancreas uses a network of ducts to connect to other organs in the digestive system, and before this work, researchers could only look at slices of ductal cancers. Those slices were often hard to interpret. In this study, the team learned that two types of cancer forms in ductal cells. One type produces ‘endophytic’ tumors, which grow towards the ducts; the other kind is ‘exophytic’ that grow outwards. The team used 3D imaging and computer modeling to learn what gave them this directionality.
“This technique revealed that cancers develop in the duct walls and either grow inwards or outwards depending on the size of the duct. This explains the mysterious shape differences that we've been seeing in 2D slices for decades,” noted Messal.
"We made a simulation of the ducts, describing individual cell geometry to understand tissue shape," explained co-lead study author and biophysicist Dr. Silvanus Alt. "The model and experimental results both confirmed that cancer grew outwards when the diameter of the duct was less than approximately twenty micrometers, around a fiftieth of a millimeter.”
The researchers used their technique to asses other organs and determined that cancers growing in lung airways and liver ducts also grow this way.
"Both the data and our models indicate that the two different mechanisms of tumor growth are purely down to the innate physics of the system," explained Dr. Guillaume Salbreux. "Like most cancers, ductal pancreatic cancer starts with a single defective cell that starts dividing. We found that very quickly when there are only a few cells; the tumor has already started to grow either inwards or outwards depending on duct diameter. Defining this fundamental process will help us to better understand how cancer grows in many places across the body."
“This technological breakthrough has the potential to unlock many unanswered questions of great importance in how we understand and treat pancreatic cancer. It's crucial we better grasp how these cancers behave from the earliest stages, to help develop treatments for a disease where survival rates have remained stubbornly low,” added Professor Andrew Biankin, a pancreatic cancer expert with Cancer Research UK.