‘Time machine’ reverses pancreatic cancer progression

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Pancreatic cancer's rapid spread and covert nature is what makes it so deadly. A time machine can reverse the progression of pancreatic cancer before it spreads to the rest of the body.

These results open up the possibility to design a new gene therapy, or drug, because we can now convert cancerous cells back to their normal state. This is according Bumsoo H., Purdue University professor of mechanical engineering and program leader at the Purdue Center for Cancer Research. Han holds a courtesy appointment as a biomedical engineer.

Hans lab created a time machine to reproduce the structure of the acinus (a pancreatic structure that produces and secretes digestive chemicals into the small intestine). Chronic inflammation is a form of pancreatic cancer that occurs when these enzymes are unable to digest the pancreas.

It would be possible to reset the pancreas if there was a way to go back and reprogram the cancerous cells in the acinar cells, which produce these enzymes.

Stephen Konieczny has been studying a reset button for the Purdues biological sciences Department for over a decade. It is a gene called PTF1a.

Normal pancreas development depends on the PTF1a gene. Konieczny states that if you don't have the PTF1a gene you won't develop a normal pancreas. Our whole idea was to see what would happen if the PTF1a gene is turned back on in a pancreatic carcinoma cell. Can we reverse the cancer phenotypes? That's exactly what happens.

Hans lab collaborated with Konieczny to bring these molecular biology findings to the next level. They tested them in a real-life model of an acinusthe machine. The journal Lab on a Chip published their findings.

Researchers often investigate pancreatic cancer treatments in animal models. However, it can take several months for pancreatic disease to develop in an animal. Researchers would be able to save time and have more control over the model if they could study cancer development in a microenvironment.

This model captures the anatomical complexity and circular cavities that are lined with cells of the acinus.

This kind of three-dimensional cavity is difficult to create from an engineering standpoint. Han says that finding a way to create this cavity was an innovative feat in engineering.

Hans lab had already built a realistic model for another pancreatic structure, called the duct. This is where cancer develops after it has emerged from the acinus. Researchers used this knowledge to develop a method that builds the duct and acinus using viscous fingering.

This is how it works: A model consisting of a glass platform the size of a postage stamp on top a microscope slide has two chambers that are interconnected. The first chamber is filled with a collagen solution. This creates the shape of a finger in the pancreatic duct. It then bulges to form the cavity structure for the acinus.

The model was made even more realistic by dropping cancerous human cells in the acinar chamber. Koniecznys lab created the PTF1a gene from a pancreatic carcinoma cell line. It was activated in the presence doxycycline (a common antibiotic compound). The cells began to build the rest of Hans' acinus, which indicated that they had been reprogrammed and were not cancerous.

This model shows that not only are the cancerous cells reprogrammed but also the normal three-dimensional architecture. It is very similar to what we see in healthy pancrease, Konieczny states.

The Hans Lab is currently testing a potential gene therapy using these findings.

The work was funded by the National Institutes of Health and the Walther Embedding Program in Physical Sciences in Oncology.

Source: Purdue University