A group of scientists has pinpointed a group of stem-like cells responsible for initiating and sustaining Group 3 medulloblastoma (Gr3-MB) in the developing brain. Gr3-MB is a highly aggressive form of brain cancer in children, often leading to metastasis and low survival rates. By targeting and eliminating this small group of stem-like cells found in Gr3-MB tumors, the researchers observed a reduction in tumor size in preclinical models. While more investigation is necessary, this innovative method could open up new avenues for treating children with Gr3-MB.
The team of researchers at Baylor College of Medicine, Texas Children’s Hospital, the Hospital for Sick Children in Toronto, and other collaborating institutions has discovered a lineage of stem-like cells responsible for the development and maintenance of Group 3 medulloblastoma (Gr3-MB) in the developing brain. Gr3-MB is one of the most aggressive forms of brain cancer in children and is linked to widespread metastasis and poor prognosis.
The researchers found that targeting the small population of stem-like cells within Gr3-MB tumors resulted in tumor shrinkage in preclinical models. While further research is needed, this groundbreaking approach could pave the way for new treatment strategies for children with Gr3-MB. The study was published in Cell.
“We believe that as Gr3-MB progresses, it retains characteristics reminiscent of embryonic development, leading to rapid tumor growth,” explained Dr. Michael D. Taylor, the corresponding author and a professor at Baylor College of Medicine and Texas Children’s Hospital. Dr. Taylor also holds the Cyvia and Melvyn Wolff Chair of Pediatric Neuro-Oncology at Texas Children’s Cancer and Hematology Center. “Our objective was to identify embryonic cells that could give rise to tumors, as well as their location and the factors driving their growth.”
The researchers compared the gene expressions in Gr3-MB cells from six tumors with those of human fetal hindbrain cells during the first trimester of pregnancy.
“We identified a lineage of embryonic stem-like cells in Gr3-MB tumors,” said Dr. Abhirami Visvanathan, the first author and a postdoctoral fellow in the Taylor lab. “These cells express a protein called protogenin that is unique to these high-risk Gr3-MB cases but absent in the normal postnatal cerebellum.”
The cancer stem-like cells were identified in a specific region of the developing cerebellum known as the rhombic lip. These cells reside in a structure unique to humans called the interposed vascular plexus. As Gr3-MB tumors develop, they recreate this vascular plexus, a feature not seen in other types of medulloblastoma.
“The stem-like cells within the tumor inhabit this immature blood vessel nest. Both tumor and vascular cells communicate with each other, creating a symbiotic environment that benefits both cell types,” Visvanathan elaborated.
A Fresh Approach to Gr3-MB Treatment
The discovery of a small population of protogenin-expressing stem-like cancer cells driving tumor growth prompted the researchers to explore a new treatment approach for Gr3-MBs.
“Instead of targeting the entire tumor, we theorized that eliminating the small group of cancer stem-like cells supporting the tumor could be beneficial, similar to dismantling an army by removing its leader,” Taylor remarked.
Consistent with the hypothesis, therapies designed to eradicate the cancer stem-like cells proved effective in animal models. “We aimed at the protogenin-expressing cells fueling tumor growth with CAR T-cell immunotherapy. CAR T-cell therapy entails modifying immune T-cells to attack a specific target, in this case, protogenin, enabling them to eliminate the cancer. This promising finding warrants further investigation to determine the efficacy of this strategy in treating human Gr3-MB.”
The study also suggests that targeting the vascular niche supporting tumor cell growth could be another potential therapeutic avenue. Additional studies are required to explore this possibility.
