Pancreatic cancer is one of the deadliest cancers, with a five-year survival rate of 7%. With early diagnosis, however, that percentage can rise to between 20% and 35%. By developing a new technology to analyze three-dimensional (3D) pancreatic tumor tissue samples, researchers have discovered ways in which the malignancies start and grow. The investigators' new technique can potentially be used for early diagnosis.
"To investigate the origins of pancreatic cancer, we spent six years developing a new method to analyze cancer biopsies in three dimensions," explained Dr. Hendrick Messal, Postdoctoral Research Assistant at the Francis Crick Institute and co-lead author of the study, which was published in Nature. "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."
The researchers used the 3D imaging technique to evaluate developing pancreatic cancer cells in mice. Using the images, the investigators discovered that there were two types of cancer formations beginning from ductal cells: endophytic tumors grow into the ducts, and exophytic tumors grow out of the ducts. In order to understand why the cancers grow in a certain way, the scientists worked in conjunction with biophysicists at the Crick Institute to analyze the 3D images and computer model simulations.
"Both the data and our models indicate that two different mechanisms of tumor growth are purely down to the innate physics of the system," stated another author of the study, Guillaume Salbreux, PhD, Group Leader of the Theoretical Physics of Biology Laboratory at the Crick Institute. "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."
When the researchers used the 3D technology on other organs, it enabled them to discover that cancers originating in lung airways and in liver ducts develop in the same way as pancreatic cancer. Applying this mechanism across various cancers can be used to increase understanding of how cancer grows in different places in the body.
Andrew Biankin, PhD, Professor and Regius Chair of Surgery at the University of Glasgow and Director of Wolfson Wohl Cancer Research Center, who was unaffiliated with the study, provided his outside perspective of this study and its importance: "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."
For More Information
Messal HA, Alt S, Ferreira RMM, et al (2019). Tissue curvature and apicobasal mechanical tension imbalance instruct cancer morphogenesis. Nature. [Epub ahead of print] DOI:10.1038/s41586-019-0891-2
Image courtesy of Hendrik A. Messal, Francis Crick Institute