Facebook Pixel Code
About Sickkids
About SickKids

May 23, 2008

Breakthrough at SickKids: How cancer stem cells ‘hide’ in tumours

Toronto - A group of investigators at The Hospital for Sick Children (SickKids) published a paper in the May 2008 issue of the journal, Stem Cells, which documents the role of hypoxia –low oxygen content – on the growth of cancer cells. Dr. Bikul Das, a research fellow in the Division of Pathology at SickKids under the primary supervision of Dr. Herman Yeger, and co-supervision of Dr. Ernest Cutz, at SickKids in collaboration with Drs. David Malkin, Gideon Koren, Sylvain Baruchel also of SickKids and, and Dr. Rika Tsuchida, a former SickKids research fellow, who is now at University of Tokyo, have demonstrated that cancer stem cells appear to hide in the low oxygen areas of the tumour and in effect, avoid the lethal effects of drug and radiation therapies. This discovery explains in part why cancers may at times recur, even after having initially responded to treatment.

Using different types of cancers, the SickKids researchers were able to demonstrate that the cancer stem cell can maintain its own identity in these hypoxic areas by upregulating two genes, Oct-4 and Nanog. Interestingly, these two genes are also involved in maintaining the identity and pluripotency of human embryonic stem cells. When the expression of Oct-4 and Nanog genes are inhibited, embryonic stem cells lose their “stemness” features and cannot grow into an embryo. In scientific terminology, the word “stemness” refers to particular characteristics of cells that determine them to be stem cells. The SickKids team was among the first to put forward an idea of a “tumour stemness switch” arguing that tumour stem cells can exploit the stemness pathway to initiate tumour growth.

These research findings are important for several reasons. First, they confirm that these tumour stem cells have the ability to hide in the hypoxic area of a tumour where drugs cannot reach them. Furthermore, these cells can sequester themselves in the liver and or bone marrow, sites that may be quite distant from where the primary tumour is found. Having identified the nature of the home for this stem cell subpopulation in tumours, we might now be in a better position to develop therapeutic approaches that could effectively target and eradicate the tumour cells responsible for eventual relapse and metastasis.

Dr. Das and his colleagues are now focusing their research on developing new techniques to either kill these cells or induce them to lose their stemness.

This interdisciplinary research was undertaken by the following individuals:

  • Dr. Bikul Das, research fellow, Division of Pathology, SickKids

  • Dr. Herman Yeger, supervisor to Dr. Das, senior scientist in the Developmental & Stem Cell Biology program at SickKids, professor in Laboratory Medicine & Pathobiology, University of Toronto

  • Dr. Ernest Cutz, co-supervisor to Dr. Dal, pathologist, senior associate scientist in the Physiology & Experimental Medicine program, SickKids, professor of Laboratory Medicine & Pathobiology, University of Toronto

  • Dr. David Malkin, co-director and staff oncologist of the Cancer Genetics Program, associate chief (Clinical) of the Research Institute, senior scientist in the Genetics & Genome Biology program at SickKids, professor of Medical Biophysics, School of Graduate Studies and in Department of Paediatrics, University of Toronto

  • Dr. Gideon Koren, senior scientist in the Child Health Evaluative Sciences program and director of the Motherisk Programs at SickKids, and professor in the Department of Paediatrics, University of Toronto

  • Dr. Sylvain Baruchel, staff oncologist in Haematology/Oncology, senior associate scientist in the Physiology & Experimental Medicine program at SickKids, and professor in the Department of Paediatrics, University of Toronto

  • Dr. Rika Tsuchida, Department of Pediatrics and Developmental Biology, Postgraduate Medical School, Tokyo Medical and Dental University, Department of Pediatrics, Faculty of Medicine, University of Tokyo