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About SickKids

April 11, 2007

Researchers develop new mouse model to better understand neuroblastoma metastasis

Researchers at SickKids have found that expression of the chemokine receptor CXCR4 makes neuroblastoma more aggressive and more metastatic in a mouse model. This link between tumour metastasis and the expression of chemokine receptors, like CXCR4, will allow researchers to develop new treatments for neuroblastoma. This research is reported in the January issue of the journal Neoplasia.

Chemokines, molecules that bind to chemokine receptors, are a family of proteins secreted by cells that facilitate communication between cells. While they are vital for normal cellular function they are also linked to the development of tumours and tumour vascularization.

It was previously found that the expression of the chemokine receptor CXCR4 is correlated with the clinical outcomes of patients with Stage IV neuroblastoma, a very deadly cancer. Dr. Sylvain Baruchel and his team conducted further investigations to determine how CXCR4 effects tumour growth and invasion.

“We found that CXCR4 expression makes neuroblastoma more aggressive and more metastatic,” says Baruchel, director of the New Agent and Innovative Therapy Program, staff oncologist, and senior associate scientist, Cancer Research.
In addition, the team discovered that the microenvironment influences how quickly neuroblastoma cells will metastasize. A microenvironment is an area where normal cells coexist with metastatic neuroblastoma cells. Neuroblastoma can take hold in a variety of different organs, such as the liver, lungs and bone marrow.

This insight will help in the development of improved prognostic markers for neuroblastoma and also increases understanding of the mechanisms behind neuroblastoma metastasis and its link with CXCR4, as well as other chemokine receptors and chemokines.

“This new mouse model of metastatic neuroblastoma allows researchers to modulate the aggressiveness of neuroblastoma, as well as the direction where cells metastasize,” adds Baruchel. “This will allow researchers to develop new additional treatments for stage IV neuroblastoma, be it through industry or via the Cancer Drug Screening Program here at SickKids.”

“There are now drugs that target cancer cells expressing CXCR4 and therefore could be use to control the rate of metastasis,” adds Dr. Libo Zhang, research associate and study lead author.

Other members of the research team included Dr. Meredith Irwin, Dr. Herman Yeger and Dr. Bikul Das, all fromSickKids. The research team would like to thank patients and families who provided samples of their tumours to be use for this study.
This research was supported by the Canadian Institutes of Health Research and the James Fund through SickKids Foundation.

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The Hospital for Sick Children