Study uncovers mechanism governing sarcoma metastasis

Vancouver, BC – Research published this week by scientists at the BC Cancer Agency in Cancer Cell brings new hope for the treatment of high-risk childhood sarcomas – a type of cancer that has seen almost no treatment improvement in the last 20 years in spite of intense research efforts.

Sarcomas are malignant tumours of the connective tissues, including bones and muscles. They are more common in children and can be extremely difficult to treat because they have a high tendency to metastasize, or spread. Up until now, there has been very little known about the mechanism of how sarcoma cells spread to other organs.

To better understand this mechanism Dr. Poul Sorensen and his team, including Dr. Amal El-Naggar, a post-doctoral fellow, studied a previously unrecognized pathway involving two proteins, YB-1 and HIF1α.

“This research shows for the first time that HIF1α production in sarcomas can be regulated by YB-1, a known drug resistance marker,” said Dr. Sorensen, distinguished scientist at the BC Cancer Agency and Professor, Department of Pathology & Laboratory Medicine and Johal chair in childhood cancer research at the University of British Columbia. “This process appears to be specific for tumour cells, which could have profound implications for targeting the YB-1-HIF1α pathway therapeutically.”

The researchers found that YB-1, which is highly expressed across virtually all human sarcoma subtypes, can directly stimulate the production of HIF1α when large tumours outgrow their blood supply and become oxygen deficient. It allows oxygen-deficient tumour cells to adapt to the stress of low oxygen (called hypoxia), making these adapted tumour cells more hardy and stress resistant, and therefore likely more treatment resistant.

They also showed that when YB-1 drives HIF1α production, this also makes sarcoma cells much more invasive and metastatic. When the process is blocked it makes local tumours more susceptible to low oxygen conditions, and also dramatically inhibits the spread of childhood sarcoma cells to the lungs.

“Dr. Sorensen’s landmark study provides real hope that dramatic improvements in the treatment of childhood sarcomas are around the corner,” said Erik Dierks, VP, development, BC Cancer Foundation.