The above image shows brain tumour stem cells that have been isolated from human brain tumours. The brain tumour stem cells are the only cells within the brain tumour that can grow are capable of forming a new brain tumour. These cells can differentiate into mature brain cells of different types such as astrocytes (red) and neurons (green). (Image courtesy of The Hospital For Sick Children)

The Hospital for Sick Children-TORONTO – Researchers at The Hospital for Sick Children (Sick Kids) and the University of Toronto (U of T) have confirmed that childhood and adult brain tumours originate from cancer stem cells and that these stem cells fuel and maintain tumor growth. This discovery has led to development of a mouse model for human brain tumors and opens the door for new therapeutic targets for the treatment of brain tumors.

“Now that we have confirmed that a small number of cancer stem cells initiates and maintains human brain tumor growth in a mouse model, we can potentially use the mouse model with each patient’s tumor cells to see if therapies are working to conquer that patient’s tumor,” said Dr. Peter Dirks, the study’s principal investigator, a scientist and neurosurgeon at Sick Kids, and an assistant professor of Neurosurgery at U of T. “A functional analysis of the brain tumor stem cell may also give new insight into patient prognosis that may then warrant individual tailoring of therapy.”

Dr. Dirks’ laboratory was able to regrow an exact replica of patients’ brain tumors in a mouse from the isolated cancer stem cells, or brain tumor initiating cells. They were then able to study the growth of the human brain tumor in the mouse model using the advanced imaging technology in the Mouse Imaging Centre (MiCE) at Sick Kids.

Brain tumors are the leading cause of cancer mortality in children and remain difficult to cure despite advances in surgery and drug treatments. In adults, most brain tumors are also among the harshest cancers with formidable resistance to most therapies.

“Next, we are going to study the gene expression of the brain tumor stem cells. Once we have identified what genes are expressed in those cells, we will then be able to target these genes using new drugs or genetic-type therapies,” said Dr. Sheila Singh, the paper’s lead author and Sick Kids neurosurgery resident and U of T graduate student who is enrolled in Sick Kids’ Clinician-Scientist Training Program. Dr. Singh was supported by a fellowship from The Terry Fox Foundation, as well as by funding from the Neurosurgical Research and Education Foundation and the American Brain Tumor Association.

“We have shown that it is really worthwhile to invest further in studying brain tumor stem cells, as we will be able to determine if current therapies are failing because they are not stopping the cancer stem cells,” added Dr. Dirks. “It also looks like cancer stem cells play a role in other solid tumors such as breast cancer, so we can all work together to develop new treatments for these cancers.”

Other members of the research team included Dr. Cynthia Hawkins, Dr. Ian Clarke, Dr. Takuichiro Hide and Dr. Mark Henkelman, all from Sick Kids, Dr. Jeremy Squire and Jane Bayani from the Ontario Cancer Institute, and Dr. Michael Cusimano from St. Michael’s Hospital.

This research was supported by the Canadian Cancer Society, the Canadian Institutes of Health Research and Sick Kids Foundation (including support from BrainChild, the Jack Baker family fund and the Jessica Durigon family fund). MiCE is supported with funding from the Canada Foundation for Innovation, Ontario Innovation Trust, the Ontario Research and Development Challenge Fund and Sick Kids Foundation.

The Hospital for Sick Children, affiliated with the University of Toronto, is Canada’s most research-intensive hospital and the largest center dedicated to improving children’s health in the country. Its mission is to provide the best in family-centered, compassionate care, to lead in scientific and clinical advancement, and to prepare the next generation of leaders in child health.


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