In mice, researchers have discovered the presence of oncostreams, highly active cells connected to how brain tumours grow and invade healthy tissue

Tumours are made up of many types of cells, both cancerous and benign.

The specific complexity of the cells inside brain tumours has been a trademark of the disease, one that makes treatment extremely difficult.

While scientists have long known about the variety of cells within a brain tumour, the ways these tumours grow has relied on the understanding that the cells are static, unmoving and relatively fixed.

But researchers at the University of Michigan Department of Neurosurgery and Rogel Cancer Center have discovered that these aggressive tumours contain highly active cells that move throughout tissue in complicated patterns. 

What’s more, the accumulations of these elongated, spindle-like cells found throughout the tumour, coined ‘oncostreams,’ serve as the basis for cancerous cells’ behaviour, determining how tumours grow and invade normal tissue.

Pedro Lowenstein, M.D., Ph.D., Richard C. Schneider Collegiate Professor of Neurosurgery and lead author of this study in Nature Communications, says this organised growth is what makes brain tumours so relentless. “Brain tumours are highly lethal, with less than 5% of patients living beyond five years,” he said. “Unfortunately, reoccurrence is what eventually kills patients. They receive surgery for their initial tumour, but the tumour always comes back within 12 to 18 months,” he said.  

Lowenstein and his team, including Maria Castro, Ph.D., also found that overexpression of Collagen 1, a protein produced by tumour cells, is essential to the growth and function of these structures.

“When we eliminated Collagen 1 production from tumour cells, the animal models with brain tumours lived much longer. This step removes oncostreams from tumours and reduces tumour aggressive behaviour because the tumours need Collagen 1 to move in the specific way we discovered,” said Lowenstein.

Lowenstein says this structure is likely present in other types of cancer, too. “Once people recognise that there are dynamic areas of the tumour, and that they’re related to tumour growth, eventual invasion and death, people will likely locate oncostreams in other tumour models,” he said.

To detect this previously unknown presence of oncostreams, the team collaborated with Todd Hollon, M.D., assistant professor in the Michigan Medicine Department of Neurological Surgery, and Sebastien Motsch, Ph.D., associate professor of mathematics at Arizona State University, to implement artificial intelligence methods to identify the structures in tissue.

“Essentially, we showed images to a computer and the computer eventually learns to recognise oncostreams,” Lowenstein explained.

Dismantling oncostreams through the removal of Collagen 1 could represent a novel therapeutic target to treat lethal brain tumours. “This research proves the crucial importance of continuing to investigate the complicated extracellular matrix,” notes Andrea Comba, Ph.D., research investigator and first author of the study.

“Based on this discovery, we propose targeting tumour collagen to disrupt oncostreams, and as novel therapy for the treatment of brain glioma,” she said.

Article: Spatiotemporal analysis of glioma heterogeneity reveals COL1A1 as an actionable target to disrupt tumor progression

Source: Michigan Medicine - University of Michigan