A “time machine” built by Purdue University engineers has shown a way to reverse the course of cancer before it spreads throughout the pancreas, according to a news release from the university.
“These findings open up the possibility of designing a new gene therapy or drug because now we can convert cancerous cells back into their normal state,” said Bumsoo Han, Professor of Mechanical Engineering and Program Leader of the Purdue Center for Cancer Research.
The time machine that Han’s lab built is a lifelike reproduction of a pancreatic structure called the acinus, which produces and secretes digestive enzymes into the small intestine. Pancreatic cancer tends to develop from chronic inflammation that happens when a mutation has caused these digestive enzymes to digest the pancreas itself.
For the past decade, Stephen Konieczny, Professor Emeritus in Purdue’s Department of Biological Sciences, has studied a potential reset button: a gene called PTF1a.
“The PTF1a gene is absolutely critical for normal pancreas development. If you lack the PTF1a gene, you don’t develop a pancreas,” Konieczny said. “So, our whole idea was, if we turn the PTF1a gene back on in a pancreatic cancer cell, what happens? Will we revert the cancer phenotype? Indeed, that’s exactly what happens.”
Konieczny collaborated with Han’s lab to take these findings in molecular biology studies to the next level by testing them in a realistic model of the acinus — the time machine. The published study is in Lab on a Chip, a journal by the Royal Society of Chemistry.
Researchers typically investigate possible pancreatic cancer treatment approaches in animal models, but it can take months for pancreatic cancer to develop in an animal. Having a way to study cancer development and treatment concepts in a microenvironment that is just as realistic would save time and give researchers more control over the model.
The model that Purdue researchers developed overcomes a major challenge in accurately capturing the anatomical complexity of the acinus, a circular cavity lined with cells.
Han’s lab already had experience building a realistic model of another pancreatic structure, the duct, where cancer grows after emerging from the acinus. The researchers took this knowledge and developed a new technique that builds both the duct and acinus in a two-step “viscous fingering” process.
Here’s how it works: The model, a postage stamp-size glass platform on top of a microscope slide, has two interconnected chambers. Loading a collagen solution into one chamber fills the finger-like shape of a pancreatic duct, which bulges and then expands to create the cavity structure of the acinus in the second chamber.
Dropping cancerous human cells into the acinar chamber made the model even more realistic. Konieczny’s lab engineered the PTF1a gene of a pancreatic cancer cell line to turn on in the presence of doxycycline, a compound commonly used in antibiotics. Once the gene was activated, the cells started constructing the rest of the acinus in Han’s model, indicating that they were no longer cancerous and had been reprogrammed.