平特五不中

The immune system can be an important ally in the fight against cancer. A study from 平特五不中 scientists published today in听Science听suggests that the reverse may also be true 鈥� that abnormal inflammation triggered by the immune system may underlie the development of stomach听tumours听in patients with a hereditary cancer syndrome known as听Peutz-Jeghers听Syndrome (PJS). The findings听are likely to听prompt听a听re-thinking of how gastric听tumours听form in patients with this syndrome听and听in听others with gastrointestinal cancers. They听should听also听open the door to potential new treatments based on targeting inflammation rather than听tumour听cells.听

A rare,听hereditary cancer syndrome听

Peutz-Jeghers听Syndrome听(PJS)听is a rare genetic disorder that affects approximately 1 in 150,000 people worldwide.听PJS is caused by a mutant, inactive version of a gene (STK11/LKB1) that acts as听a听tumour听suppressor听and regulator of cell growth,听metabolism, survival and polarity (the way the different elements in the cell are organized).听Initial signs of the disease are听the development of听dark blue or brown freckles听around people鈥檚 mouths, eyes,听and听nostrils. Patients also develop听benign polyps听鈥� masses听of cells that form on the inside lining of their stomach and听their digestive tract.听听

By听the听age听of听65, those with the syndrome have听a greater than听90 percent chance of developing cancer, including听pancreatic, stomach, ovarian, cervical, colon or听breast cancer.听There is currently no cure for PJS.听Patients are monitored for cancer听development and听often听require听surgery to remove polyps to prevent intestinal blockage听and听bleeding.听听

Researchers听looking for a cure for听PJS听have听long听focused on the听role that听the听STK11听gene听plays听in the听epithelial cells of the gastrointestinal tract where polyps,听and听eventually听tumours,听form.听But a serendipitous discovery in mice led 平特五不中-based researchers听to turn their attention in a听completely different听direction听鈥� the immune system.听

A new focus on the immune system听

Dr.听Julianna听Blagih, who听was听studying the听role of听STK11/LKB1听in听immune cells as part of听her Ph.D.听thesis听at 平特五不中,听observed that mice with disruption of the听STK11听gene only in T cells听鈥� soldiers of the immune system that protect our bodies from infection 鈥撎齞eveloped gastrointestinal听tumours听similar to those found in people with PJS.听This observation led Dr.听Blagih听and听her Ph.D. supervisor,听Dr.听Russell Jones, to explore听how听immune听cells听may contribute to听development of听the disease.听听

鈥淭his is a great听example of how a random discovery in听fundamental science in听the lab can lead to new ideas about how diseases are caused, and potentially also to new treatments,鈥澨齭aid听Dr.听Jones,听corresponding author of the study and听Associate Professor in the Department of Physiology and the听Goodman Cancer Research Centre at 平特五不中. 鈥淲hen we听investigated further, we听confirmed听that听these were not simply random results听and听that听the mice with T cells with听these听mutations听developed听inflammation听in their听gastrointestinal听tract听and polyps similar to those in PJS patients.鈥澨�听听

Moreover,听Dr. Maya Poffenberger,听the lead author and a member of Dr. Jones鈥� research team,听discovered that听telltale signs of inflammation were found in polyps from human PJS patients. She also found听that听polyp听development could be reduced in听genetically-susceptible mice when they were administered听medication that interrupted听specific inflammatory pathways.听

Changing paradigms听for听Peutz-Jeghers听Syndrome听

Dr. Jones听adds, 鈥淏asically,听our work听changes听the听way we have been thinking听about this disease, with our focus now on understanding how the immune system听contributes to polyp development.听We hope that our discovery will听lead to new treatments听for听PJS听patients听and others with听gastrointestinal cancers.听We鈥檙e pretty excited about it.鈥澨�听

Dr. Jones鈥櫶齨ext step is to work with mouse听models and听to听continue听collaborations听with听colleagues such as听George Zogopoulos and听William Foulkes at the 平特五不中 Health Centre (MUHC)听to study听in听patients听the听role of inflammation in the disease.听

To read 鈥溾�� by听M. C. Poffenberger et al听in听Science

The research was funded by听the Canadian Cancer Society,听the Canadian Institutes of Health Research (CIHR), the 平特五不中 Integrated Cancer Research Training Program,听and听the Fonds de Recherche du Qu茅bec 鈥� Sant茅 (FRQS).听

About the Goodman Cancer Research Centre听
The听听(GCRC), located within 平特五不中鈥檚 Life Sciences Complex, is a state of the art hub for groundbreaking cancer research that attracts and retains top scientists from around the world.听听Originally established in 1978 as the 平特五不中 Cancer Centre, the Centre leads scientific advances that enable us to investigate cancer at a genomic, cellular and molecular level, and understand how cancer progresses, spreads and resists therapies. The Centre currently comprises 27 dedicated research teams with cutting-edge technology platforms, research and support staff and over 200 trainees. Research activities at the GCRC represent a first line of defense in the fight against cancer, with focus on fundamental research to understand why cancers fail to respond to treatment and translating findings into new targets and therapies.听

Contacts:听
Russell Jones,听Goodman Cancer Research Centre, Department of听Physiology, 平特五不中,听russell.jones [at] mcgill.ca,听Twitter: 听(English interviews)听

Nicole Beauchemin,听Goodman Cancer Research Centre, Department of听Physiology, 平特五不中,听Nicole.beauchemin [at] mcgill.ca听(French interviews)

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Photo听caption:听Artist rendition of a growing stomach polyp from a听Peutz-Jeghers听Syndrome patient. The red cells represent pro-inflammatory T cells听that promote听polyp development. Artist credit: Ella Maru Studio.听

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