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The picture shows a cancer developing inside the pancreatic duct of a mouse. It was obtained with the help of a new 3D tissue study technique, revealing that cancers can start with "endophytic" tumors that develop in the channels (shown here) or from exophytic tumors developing outwards. Credit: Hendrik Mbadal, Francis Crick Institute
A new technique for studying 3D tissue samples has revealed that pancreatic cancers can develop and develop in two different ways, solving a decades-old mystery about tumor formation.
The new method could help researchers obtain more information from tissue biopsies and could help improve pancreatic cancer treatments. The technique was developed by scientists at the Francis Crick Institute and their results are published in the Nature. The work was supported by the European Research Council and a lead funding from Cancer Research UK, the Medical Research Council and Wellcome.
The pancreas is an essential organ that lies behind our stomach and plays a key role in digestion. It is based on a network of ducts linking it to other digestive organs, and the most common pancreatic cancers are found in ducts. However, until now, only 2D sections of these ductal cancers, containing an unexplained variety of abnormal forms, were possible.
"To study the origins of pancreatic cancer, we spent six years developing a new method of badyzing three-dimensional cancer biopsies," says Dr. Hendrik Messal of the Francis Crick Institute, co-author of the research. "This technique revealed that cancers develop in the walls of the cbads and grow either inwards or outwards, depending on the size of the cbad, which explains the mysterious differences in shape that we have been observing in 2D slices for decades. "
By badyzing cancers developing in 3D, the team has defined two distinct types of cancer formation from ductal cells: "endophytic" tumors that develop in the "exophytic" ducts and tumors that develop towards # 39; outside. To discover what makes cancer cells develop in a particular way, they badyzed detailed 3D images and worked with Crick biophysicists, who created sophisticated computer models.
"We did a simulation of the channels, describing the geometry of individual cells to understand the shape of the tissues," says biophysicist Dr. Alt Silvanus, co-lead author of the article. "The model and the experimental results both confirmed that the cancer was growing outward when the duct diameter was less than about twenty microns, about one-fiftieth of a millimeter."
The work was made possible thanks to an interdisciplinary collaboration between two Crick research groups, led by Dr. Axel Behrens and Dr. Guillaume Salbreux. Axel's group works on stem cells and pancreatic cancer, while Guillaume focuses on the use of physics to understand biological processes.
"I think we started talking about it as soon as we met in the bike garage," says Axel. "It's amazing what can come from a chance encounter, and now we have a patented technique to visualize the three-dimensional forms of cancer and a biophysical understanding of the emergence of tumors." We now know that cancer pancreas can develop in two different ways. " we can start looking for it is likely that we will be more aggressive or we will spread in another way. This could, in several years, improve the options of diagnosis or treatment. "
The team also applied the technique to other organs and found that cancers of the airways of the lungs and liver ducts behaved in the same way. This shows that the mechanism discovered by the teams is not specific to the pancreas and also applies to other cancers.
"The data and our models indicate that the two different mechanisms of tumor growth are purely due to the innate physics of the system," says Dr. Guillaume Salbreux. "Like most cancers, pancreatic ductal cancer begins with a single defective cell that begins to divide, and we found that very soon, when there are more than a few cells, the tumor has already started to grow inward or outward, depending on the diameter of the cbad.Final process will help us better understand how cancer develops in many places of the body. "
Professor Andrew Biankin, cancer research UK cancer pancreas cancer expert, said: "This technological breakthrough could solve many important issues in the understanding and treatment of pancreatic cancer. It is crucial to better understand how these cancers behave in the early stages, to help develop treatments for an illness where survival rates have remained stubbornly low. "
This article has been republished from documents provided by the Francis Crick Institute. Note: Content may have changed for length and content. For more information, please contact the cited source.
Reference: Hendrik A. Messal, et al. The curvature of tissues and the imbalance of apicobasal mechanical tension explain the morphogenesis of cancer. Nature. DOI: https://doi.org/10.1038/s41586-019-0891-2
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