Receptor protein prevents new tumors in mouse model of glioblastoma

Cerebellar stem cells that give rise to aggressive brain cancers, such as medulloblastoma
California Institute for Regenerative Medicine

Glioblastoma is a brain cancer well known for its aggressive cellular growth, resistance to chemotherapy and poor mortality after diagnosis. Now, researchers at Ottawa Hospital Research Institute have shown that the cancer’s stubborn behavior depends on a key protein called the oncostatin M receptor, which may lead groups to target OSMR for the treatment of glioblastoma.

Lead author Arezu Jahani-Asl performed most of the work at the University of Ottawa with co-supervisors Michael Rudnicki from Ottawa and Azad Bonni from Harvard Medical School and the Washington University School of Medicine. They published their findings earlier this week in the journal Nature Neuroscience.

The most effective treatment for this tumor is surgical resection. However, if a tumor stem cell remains around the border of the resection, there is a risk these stem cells can form a whole new tumor. By blocking OSMR activity, the researchers were able to prevent these remaining stem cells from forming new tumors in mouse brains.

"Being able to stop tumor formation entirely was a dramatic and stunning result," Rudnicki said in a news release. "It means that this protein is a key piece of the puzzle, and could be a possible target for future treatments."

They also looked at 339 tumor samples from patients who died from glioblastoma. They found that the higher the expression of OSMR transcripts the faster the patient succumbed to the cancer. This was further validated in mice, in which they injected human brain tumor stem cells with an OSMR gene knockdown. The result, as they had predicted, was improved survival.

"This study raises the exciting prospect of potential new targets for a lethal disease," Bonni said in the release. "The next step is to find small molecules or antibodies that can shut down the protein OSMR or stop it from interacting with EGFR. But any human treatment targeting this protein is years away."

- here’s the release
- here’s the journal abstract

Image of cerebellar stem cells courtesy of California Institute for Regenerative Medicine.