Uncovering how injury to the pancreas impacts cancer formation
Date:
October 29, 2021
Source:
Vanderbilt University
Summary:
Pioneering research shows that acinar cells in the pancreas form
new cell types to mitigate injury but are then susceptible to
cancerous mutations.
FULL STORY ========================================================================== Pioneering research from scientists at the Vanderbilt University School
of Medicine Basic Sciences and the Salk Institute for Biological Studies
shows that acinar cells in the pancreas form new cell types to mitigate
injury but are then susceptible to cancerous mutations.
==========================================================================
This research, led by Kathy DelGiorno, assistant professor of cell
and developmental biology at the School of Medicine Basic Sciences,
Geoffrey Wahl, professor in the Gene Expression Laboratory and holder
of the Daniel and Martina Lewis Chair at the Salk Institute, and first
author Zhibo Ma, postdoctoral fellow in the Wahl lab, was published in Gastroenterology on October 22.
The findings establish a "better understanding of the mechanisms of
healing in the pancreas and when these processes go awry," DelGiorno
said. The team used a multidisciplinary approach that combined single-cell
RNA sequencing, ultrastructural microscopy, genetically engineered models,
and patient samples to identify the cell types that form in response to pancreatic injury.
Vanderbilt contributions included computational analysis by Ken Lau,
associate professor of cell and developmental biology, and various
microscopy approaches by Dylan Burnette, associate professor of cell and developmental biology, and Rafael Arrojo e Drigo, assistant professor
of molecular physiology and biophysics.
From this approach, "we compared our dataset to published datasets
of gastric injury, oncogene-induced pancreatic neoplasia, and human pancreatitis to identify conserved processes across species and organ
systems," said DelGiorno.
According to Wahl, the findings of this paper "support our long-held
thesis that tissue inflammation causes cells to reprogram to a more
primitive, developmentally plastic state that under normal circumstances contributes to tissue repair. When subverted by oncogenes like RAS in
pancreas cancer, it causes one of the most incalcitrant cancers known to medical science." Why It Matters Pancreatic cancer is a major public
health burden and is slated to become the second-leading cause of cancer-related deaths in the U.S. by the year 2030.
Currently, the average five-year survival rate for pancreatic cancer is
only 10 percent, one of the worst of any cancer type. New and innovative treatments are greatly needed to change these outcomes for pancreatic
cancer patients.
"Our work captured how these acinar cells change in response to injury
with incredible resolution. We've been able to identify multiple diverse
cells generated by the acinar cells and uncover where they came from. Our findings provide a valuable resource to the field of pancreatic cancer
research for understanding the processes that happen early in pancreas
injury and tumorigenesis," Ma said.
"We hope to co-opt and/or target these processes for the benefit of
patients needing treatment for pancreatitis and cancer," DelGiorno said.
What's Next? The Vanderbilt team has received a National Institute of
General Medical Sciences Maximizing Investigators' Research Award to
follow up on this work.
"We will be using genetically engineered models to study the lineage trajectories and functional role of the cell types identified in this
study," DelGiorno said. "We will identify the physiological role of
these cell types in pancreatic injury, regeneration, and tumorigenesis." ========================================================================== Story Source: Materials provided by Vanderbilt_University. Original
written by Aaron Conley.
Note: Content may be edited for style and length.
========================================================================== Journal Reference:
1. Zhibo Ma, Nikki K. Lytle, Bob Chen, Nidhi Jyotsana, Sammy Weiser
Novak,
Charles J. Cho, Leah Caplan, Olivia Ben-Levy, Abigail C. Neininger,
Dylan T. Burnette, Vincent Q. Trinh, Marcus C.B. Tan, Emilee
A. Patterson, Rafael Arrojo e Drigo, Rajshekhar R. Giraddi,
Cynthia Ramos, Anna L.
Means, Ichiro Matsumoto, Uri Manor, Jason C. Mills, James
R. Goldenring, Ken S. Lau, Geoffrey M. Wahl, Kathleen
E. DelGiorno. Single-cell transcriptomics reveals a conserved
metaplasia program in pancreatic injury. Gastroenterology, 2021;
DOI: 10.1053/j.gastro.2021.10.027 ==========================================================================
Link to news story:
https://www.sciencedaily.com/releases/2021/10/211029103155.htm
--- up 8 weeks, 1 day, 8 hours, 25 minutes
* Origin: -=> Castle Rock BBS <=- Now Husky HPT Powered! (1:317/3)