Researchers from Baylor College of Medicine, Texas Children’s Hospital, the Hospital for Sick Children in Toronto, and other institutions have identified a possible treatment strategy for metastatic medulloblastoma, according to a publication in Nature Cell Biology. The study reveals a communication mechanism between metastatic medulloblastoma and fibroblasts in the leptomeninges, the membranes that cover the brain and spinal cord. This interaction recruits and reprograms leptomeningeal fibroblasts to support tumor growth, suggesting that disrupting this communication might offer a treatment method for this aggressive disease.
"Metastases, the spreading of a tumor away from its original site, are the most common and most important cause of illness and death for children with medulloblastoma," said Dr. Namal Abeysundara, a co-first author of the study and postdoctoral fellow at the Arthur and Sonia Labatt Brain Tumor Research Center and the Developmental and Stem Cell Biology Program at the Hospital for Sick Children in Toronto. Michael D. Taylor, the corresponding author, holds positions at Baylor and Texas Children’s Hospital.
The research team examined the interaction between metastatic medulloblastoma cells and leptomeningeal fibroblasts. "We discovered previously unknown interactions in the leptomeninges that facilitate the spread and growth of medulloblastoma," explained Dr. Abeysundara. Metastatic cells secrete PDGF protein, recruiting fibroblasts which then transform into tumor-supporting meningeal fibroblasts.
These reprogrammed fibroblasts differ from normal ones by secreting proteins BMP4 and BMP7, which promote tumor colonization and spread. "We were most excited about the discovery of a novel intercellular communication cascade involving PDGF and BMP signaling," noted Dr. Abeysundara, adding that understanding such mechanisms is crucial.
The study showed blocking the PDGF signal in animal models improved survival, supporting the approach of targeting tumor-microenvironment communication as a treatment strategy.
Dr. Abeysundara indicated that these findings might extend to other cancers like melanoma, breast, and lung cancers, which also metastasize to the leptomeninges.
Michael D. Taylor added, "Our research uncovered a hidden communication network in the brain's protective layers that helps medulloblastoma spread. This novel discovery shows how tumor cells and non-tumor cells work together to create an environment that supports tumor growth, offering new insights into the complexity of medulloblastoma progression."
For a comprehensive list of contributors, affiliations, and study funding, refer to the published paper.
