In a new study, researchers from McGill University suggest that abnormal inflammation triggered by the immune system may help develop stomach tumors.
The tumors grow in patients with a hereditary cancer syndrome known as Peutz-Jeghers Syndrome (PJS).
PJS is a rare genetic disorder that affects approximately 1 in 150,000 people worldwide.
It is caused by a mutant, inactive version of a gene (STK11/LKB1) that acts as a tumor suppressor and regulator of cell growth, metabolism, survival, and polarity (the way the different elements in the cell are organized).
Initial signs of the disease are the development of dark blue or brown freckles around people’s mouths, eyes, and nostrils.
Patients also develop benign polyps—masses of cells that form on the inside lining of their stomach and their digestive tract.
By the age of 65, those with the syndrome have a greater than 90 percent chance of developing cancer, including pancreatic, stomach, ovarian, cervical, colon or breast cancer.
There is currently no cure for PJS. Patients are monitored for cancer development and often require surgery to remove polyps to prevent intestinal blockage and bleeding.
Previous research looking for a cure for PJS have focused on the role of the STK11 gene in the gastrointestinal tract where polyps and eventually tumors occur.
In the current study, the researchers turned their attention in a completely different direction—the immune system.
They had observed that mice with disruption of the STK11 gene only in T cells—soldiers of the immune system that protect our bodies from infection—developed gastrointestinal tumors similar to those found in people with PJS.
That observation led them to explore how immune cells may contribute to the development of the disease.
They also found that polyp development could be reduced in genetically-susceptible mice when they were administered medication that interrupted specific inflammatory pathways.
The team suggests their work changes the way people have been thinking about this disease.
The finding may lead to new treatments for PJS patients and others with gastrointestinal cancers.
Their next step is to work with mouse models to study in patients the role of inflammation in the disease.
her Ph.D. supervisor, Dr. Russell Jones is the corresponding author of the study and Associate Professor in the Department of Physiology and the Goodman Cancer Research Centre at McGill.
Dr. Maya Poffenberger is the lead author and a member of Dr. Jones’ research team.
Dr. Julianna Blagih, who was studying the role of STK11/LKB1 in immune cells as part of her Ph.D. thesis at McGill, is one author of the research.
The study is published in Science.
Copyright © 2018 Knowridge Science Report. All rights reserved.
Journal reference: “LKB1 deficiency in T cells promotes the development of gastrointestinal polyposis” Science (2018). science.sciencemag.org/cgi/doi … 1126/science.aan3975
