New target found for common pediatric brain tumor

MRI image of medullablastoma--Courtesy of NIH.

Researchers have discovered what appears to be an essential growth factor associated with medulloblastoma, the most common malignant brain tumor in children, a finding that could help scientists better target these tumors to provide more effective and less damaging treatments.

A team led by Massachusetts General Hospital researchers found that blocking this newly discovered molecular pathway--which involves interactions between tumor cells and the surrounding tissues--made all four molecular subtypes of medulloblastoma regress in several mouse models.

These invasive tumors grow rapidly and account for about 20% of all pediatric brain tumors. When treated with existing methods--surgery, chemotherapy and radiation--patients live longer but often suffer long-term developmental, behavioral, and neurological side effects, especially in very young patients.

The study shows that when expressed, PIGF--a naturally occurring protein that belongs to the family of vascular endothelial growth factors (VEGF) and promotes the formation of blood vessels--plays a role in the growth and spread of medulloblastoma.

"Our finding that a pathway carrying signals from host cells to tumor cells via placental growth factor and its receptor neuropilin 1 is critical to the growth of medulloblastoma, regardless of molecular subtype, strongly supports evaluating antibodies against these proteins as a novel therapeutic approach to this pediatric cancer," said Rakesh Jain, director of the Steele Laboratory for Tumor Biology at Massachusetts General Hospital and one of the study's authors, in a statement. 

Researchers conducted studies in several mouse models and found that the presence of PlGF is essential to the progression of medulloblastoma. Using several antibodies against the growth factor effectively reduced tumor growth and spread and increased animal survival.

Most PlGF was produced by surrounding supportive tissue called stroma and not by the tumor cells, researchers found. Furthermore, they observed that when tumor cells released the developmental protein Shh, it causes the expression in nearby stromal cells of PlGF, which then binds to the Nrp1 receptor on tumor cells and spurs more tumor growth. Blocking this interaction between PlGF and Nrp1 could provide a more targeted treatment method than therapies that just target mutations that drive tumor growth. The findings were recently published in the journal Cell.

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