Scientists have engineered human pancreatic cancer cells (Panc-1) to reprogram and revert them back to their normal state following PTF1A gene expression. They achieved this using a novel in vitro model called pancreatic acinus-on-chip (PAC). Their findings were published in Lab on a Chip, a journal by the Royal Society of Chemistry.
The pancreas is an organ in the abdomen that lies behind the lower part of the stomach. It is both an exocrine and an endocrine organ. The exocrine pancreas, in particular, plays an essential role in digestive processes, as it is responsible for the secretion of digestive enzymes, ions and water into the duodenum of the gastrointestinal tract.
The pancreatic acinus is the functional unit of the exocrine pancreas. It is made up of clusters of cells that produce and secrete digestive enzymes. The pathobiology of the pancreas acinus is crucial to pancreatic disease, including pancreatitis and pancreatic cancer.
Unfortunately, pancreatic cancer is extremely deadly. Many patients do not receive a diagnosis until the disease has spread outside of the pancreas, and the five-year survival rate for all stages of the cancer is just 9%. Pancreatic cancer is so damaging largely due to its covertness and ability to quickly metastasise. Moreover, historically, research on the pancreatic acinus has been significantly hampered due to the difficulties of culturing normal acinar cells in vitro.
Creating the pancreatic ‘time machine’
Recently, mechanical engineers at Purdue University developed an in vitro model, called pancreatic acinus-on-chip (PAC), to help overcome some of the challenges faced when studying pancreatic cancer. The PAC is a small glass platform on top of a microscope slide and is controlled by a ‘viscous-fingering’ technique. The researchers used this platform as a realistic model of the acinus as it had two interconnected chambers. This was able to mimic the finger-like shape of the pancreatic duct and cavity structure of the acinus.
The PAC – a glass platform on a microscope slide consisting of two interconnected chambers, resembling the anatomical structures involved in the spread of pancreatic cancer. Image credit: Perdue University
The scientists engineered human pancreatic cancer cells (Panc-1) and added them into the acinar chamber. They then activated the expression of PTF1A. PTF1A encodes for a pancreas associated transcription factor, and mutations of this gene have been associated with pancreatic cancer.
After the induced expression of PTF1A, it was found that the Panc-1 cells transitioned into differentiated acinar phenotypes. This indicated that these cells were no longer cancerous and had in fact been reprogrammed. A so-called ‘time machine’ had been developed to reverse the course of pancreatic cancer.
Stephen Konieczny, Professor Emeritus at the University of Perdue, explained:
“The PTF1A gene is absolutely critical for normal pancreas development. If you lack the PTF1A gene, you don’t develop a pancreas. 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.”
The prospect of reprogramming cancer cells
Researchers typically investigate the molecular mechanisms behind pancreatic cancer in animal models. But it can take months for pancreatic cancer to develop in an animal, making this approach slow and ineffective. The development of the PAC model provides a new and reliable method for studying the initiation and progression of pancreatic disorders. By accurately capturing the anatomical complexity of the acinus, researchers can gain a clearer understanding of pancreatic cancer biology and use this information to explore possible diagnostic tests or gene therapies.
Bumsoo Han, Professor at the University of Perdue and developer of PAC, said: “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.”
Image credit: Oncology Nurse Advisor