Wednesday, 06 October 2021 08:59

Pancreatic cancer undone in human cells Featured

A team of researchers at Purdue University in West Lafayette, Indiana, engineered an acinar-on-chip (PAC) from reprogrammed pancreatic cancer cells and induced PTF1a gene expression in the cells. They observed that the cells transitioned to a more normal and differentiated acinar phenotype. The model can be used to study the development and progression of pancreatic cancer.

For their studies, the team led by Prof. Bumsoo Han recreated a specific structure of the pancreas, the acinus. An acinus is one of the numerous glandular endings of the pancreas - a small functional unit. It consists of pyramidal epithelial cells (acinar cells) arranged in a cell layer concentrically around the small central glandular lumen. This is where the digestive secretions* are drained.

Changes in the acini can lead to pancreatic cancer. So far, it has been difficult to grow normal acinar cells in vitro to conduct mechanistic studies. The scientists have now succeeded in doing this by converting cancer cells back into normal acinar cells and culturing them in a special microfluidic platform with epithelial channel and acinar sac geometry for studies.

The researchers replicated the acinar structures in a glass slide.
Photo: Purdue University/John Underwood

The lynchpin for the reverse transformation was the protein PTF-1a, the Pancreatic transcription factor 1, subunit a. It plays a role in the development of the pancreas. Loss of protein expression is observed in pancreatic ductal carcinomas. The team has taken advantage of this by switching the gene for the transcription factor back on.

“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 Prof. Han, director of the Purdue Center for Cancer Research, in the press release.

Original publication:
Stephanie M. Venis, Hye-ran Moon, Yi Yang, Sagar M. Utturkar, Stephen F. Konieczny & Bumsoo Han (2021). Engineering of a Functional Pancreatic Acinus with Reprogrammed Cancer Cells by Induced PTF1a Expression. Lab on a Chip.