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3D images reveal how the pancreatic cancer begins

The picture shows a cancer that grows in the pancreas of a mouse. It was obtained using a new technique for the study of tissue samples from 3D, revealing that cancer can begin as 'endophytic' tumors that grow in the channels (shown here) or 'exophytic' tumors growing outward. Credit: Hendrik Masal, Frances Creek Institute

A new technique for the study of tissue samples in 3D revealed that pancreatic cancer can begin and grow in two different ways, solving a decade-long mystery of how tumors form.

The new method can help researchers get more information from a tissue biopsy and can lead to better treatments for pancreatic cancer. The technique was developed by the scientists at the Francis Creek Institute, and their results are published in Nature. The work was supported by the European Council for Research and Fixed Assets from Research Cancer UK, the Medical Research Council and Wellcome.

The pancreas is a key organ that sits behind the stomach and plays a key role in digestion. It relies on a network of channels that link it to other digestive organs, and the most common pancreatic cancers are found in the canals. However, by now it is only possible to see 2D fragments of these ductal carcinomas, which contained unexplained varied abnormal forms.

"To investigate the origin of pancreatic cancer, we spent six years developing a new method for analyzing cancer biopsies in three dimensions," explains Dr. Hendrik Messal of the Francis Creek Institute, a co-leader of the research paper. "This technique revealed that the cancer develops in the walls of the channels and grows either inwards or outward, depending on the size of the channel. This explains the mysterious differences in the forms we see with 2D pieces for decades."

By analyzing the development of cancer in 3D, the team defines two distinct types of cancer formation arising from ductal cells: endophytic & lt; tumors that grow in channels and exophytic & lt; tumors that grow outward. To find out what makes the cancer cells in a certain way, they analyzed detailed 3D images and worked with biophysics in Creek, which created sophisticated computer models.

"We made a channel simulation, describing the individual cell geometry to understand the shape of the tissue," explains biophysicist Dr. Silvanus Alt, co-founder of labor. "The model and experimental results confirmed that the cancer grew outward when the diameter of the canal was less than about twenty micrometers, about fifteen millimeters."

The work was made possible through interdisciplinary co-operation between two Scream research groups led by Dr Axel Berens and Dr Guillaume Salbro. The Axel group works on stem cells and pancreatic cancer, while Guillaume focuses on using physics to understand biological processes.

"I think we started talking about this for the first time when we collided with each other at a bicycle school," Axel says. "It's amazing that it can come out of a random meeting, we now have a patented technique to see three-dimensional forms of cancer and a biophysical understanding of the occurrence of tumors. Now that we know that pancreatic cancer can develop in these two different ways, we begin to consider whether someone is likely to be more aggressive or to spread in a different way. For many years now, this can lead to improved diagnostic or treatment options. "

The team also applied the technique to other organs and found that airway cancer in the lungs and liver channels behaved the same way. This shows that the mechanism discovered by the teams is not specific to the pancreas, and also applies to other types of cancer.

"The data and our models suggest that the two different mechanisms of tumor growth are purely down to the innate physics of the system," explains Dr Guillaume Salbro. "Like most cancers, the ductal pancreatic cancer begins with a defective cell that begins to divide. We found that very quickly, when there are only a few cells, the tumor has already begun to grow either in or out, depending on the diameter of the channel. the process will help us better understand how cancer grows in many places throughout the body. "

Professor Andrew Biankin, an expert on pancreatic cancer cancer research, said: "This technological breakthrough has the potential to unlock many unanswered questions of great importance in the way we understand and treat pancreatic cancer. It is crucial to understand how these cancer is at the earliest stages, to help develop the treatment of disease where survival rates remain stubbornly low. "

This article is published by materials provided by the Francis Creek Institute. Note: The material may be arranged for length and content. For more information, please contact the source.

Reference: Hendrik A. Messal, et al. The tissue curve and apicoasal mechanical tension imbalance cite cancer morphogenesis. Nature. DOI: https://doi.org/10.1038/s41586-019-0891-2

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