Cancer and Immunity: Dr. Jekyll and Mr. Hyde in Single Proteins
The story of Dr. Jekyll and Mr. Hyde, about the positive and negative aspects of the same person, could also apply to proteins. Cellular inhibitor of apoptosis proteins (IAPs), are known to have negative effects by promoting the development of many cancers. However, a recent study suggests that these proteins may also play an important positive role by helping to activate the immune system that prevents bacterial and viral infection.
This discovery could have a major impact in the treatment of both cancer and immune dysfunction. The findings will be published in the June issue of Immunity in a paper by Dr. Maya Saleh, of the Research Institute of the McGill University Health Centre (MUHC) and McGill University, and Dr. Phil Barker, of the Montreal Neurological Institute (MNI) and McGill University.
Researchers have known for several years that IAPs promote abnormal cell survival, which is an important feature of cancer cells. Medications are currently being developed that specifically target IAPs in order to make cancer cells die.
The study by Drs. Saleh and Barker is intriguing because it shows that these same proteins normally have a very different function. “Our study reveals that IAPs play a crucial role in the normal function of the innate immune system,” states Dr. Saleh. The IAPs help mount the first line of defense that the body uses to protect itself against invading pathogens: the inflammation process.
“We studied mice that were genetically modified so that they did not express specific IAPs ,” explains Dr. Barker. “Our analyses proved that these animals showed a weaker innate immune response when exposed to molecules found on bacteria." This proves that the IAPs may normally help protect the body from infection by regulating and stimulating inflammation.
The pivotal role of those proteins raises the possibility that the IAPs may be important in promoting some types of inflammatory conditions. Drugs that target the IAPs show great promise for the treatment of cancer and this latest research indicates that targeting the IAPs may also be useful for modulating responses of the immune system.
Funding
This study was funded by grants from the Canadian Institutes of Health Research (CIHR). The researcher’s salaries were funded by grants from McGill University, the Fonds de la recherche en santé du Québec, the CIHR, and the Jean Timmins Costello Foundation.
Dr. Maya Saleh is a researcher with the Critical Care Division and the Centre for the Study of Host Resistance at the Research Institute of the McGill University Health Centre (MUHC) as well as an Assistant Professor with McGill University’s Faculty of Medicine.
Dr. Phil Barker is the Associate Director for Strategic Planning at the Montreal Neurological Institute (MNI) and a coordinator of the MNI’s Centre for Neuronal Survival. He is a Professor in the Departments of Neurology & Neurosurgery and Anatomy & Cell Biology at McGill University.
Partners
This study was co-authored by Mathieu J.M. Bertrand (MNI, McGill University), Karine Doiron (MUHC, McGill University), Katherine Labbé (MUHC, McGill University), Robert G. Korneluk (Children's Hospital of Eastern Ontario), Philip A. Barker (MNI, McGill University), and Maya Saleh (MUHC, McGill University).
The Research Institute of the McGill University Health Centre (RI MUHC) is a world-renowned biomedical and health-care hospital research centre. Located in Montreal, Quebec, the institute is the research arm of the MUHC, the university health center affiliated with the Faculty of Medicine at McGill University. The institute supports over 600 researchers, nearly 1200 graduate and post-doctoral students and operates more than 300 laboratories devoted to a broad spectrum of fundamental and clinical research. The Research Institute operates at the forefront of knowledge, innovation and technology and is inextricably linked to the clinical programs of the MUHC, ensuring that patients benefit directly from the latest research-based knowledge. The Research Institute of the MUHC is supported in part by the Fonds de la recherche en santé du Québec.For further details visit: www.muhc.ca/research.
About the Montreal Neurological Institute and Hospital: The Montreal Neurological Institute and Hospital (The Neuro) is a unique academic medical centre dedicated to neuroscience. The Neuro is a research and teaching institute of McGill University and forms the basis for the Neuroscience Mission of the McGill University Health Centre. Founded in 1934 by the renowned Dr. Wilder Penfield, The Neuro is recognized internationally for integrating research, compassionate patient care and advanced training, all key to advances in science and medicine. Neuro researchers are world leaders in cellular and molecular neuroscience, brain imaging, cognitive neuroscience and the study and treatment of epilepsy, multiple sclerosis and neuromuscular disorders. For more information, please visit www.mni.mcgill.ca.