Targeting Stem-Like Cells Shrinks Medulloblastoma Tumors in Preclinical Study

New Study Identifies Stem-Like Cells in Aggressive Childhood Brain Cancer

A group of researchers from Baylor College of Medicine, Texas Children’s Hospital, the Hospital for Sick Children in Toronto, and collaborating institutions have discovered a small population of stem-like cells that initiates and maintains a highly aggressive form of brain cancer in children. The study, published in Cell, highlights a potential novel approach to treat children diagnosed with Group 3 medulloblastoma (Gr3-MB), which has a high risk of metastasis and leads to poor survival rates.

Identification of Embryonic Stem-Like Cells

As Gr3-MB tumor grows rapidly, researchers hypothesized that the cancer sustains characteristics present in embryonic development. The team compared genes expressed by Gr3-MB cells from six tumors with those expressed by human fetal hindbrain cells during the first trimester of pregnancy. They found a lineage of embryonic stem-like cells in Gr3-MB tumors that expresses a protein known as protogenin. These protogenin-expressing cells were present only in these high-risk tumors but absent in normal postnatal cerebellum.

Location and Factors that Drive the Growth of Gr3-MB

The researchers located the cancer stem-like cells in a specific brain region called the rhombic lip. This region is unique to humans and is embedded in a structure known as the interposed vascular plexus. When Gr3-MB tumors develop, they recreate the vascular plexus. Other types of medulloblastoma do not have this unique vascular structure, and this finding provides a promising approach to explore the possibility of targeting the vascular niche that supports tumor cell growth as a potential therapeutic option.

New Potential Therapeutic Approach

The study revealed that stem-like cells in the tumor live in this immature blood vessel nest. Both tumor and vascular cells talk to each other and maintain a symbiotic niche benefiting both cells. The researchers hypothesized that instead of attacking the entire tumor, eliminating the small population of cancer stem-like cells that sustains the tumor would be therapeutic. The approach is analogous to triggering the dissolution of an army by removing the leader.

Therapies directed at eliminating the cancer stem-like cells produced effective results in animal models. The researchers targeted the protogenin-expressing cells that sustain tumor growth with CAR T-cell immunotherapy, a promising strategy in which immune T-cells are modified to attack a specific target – protogenin in this case – enabling them to kill the cancer. This research supports further investigations to determine whether this strategy is effective in treating human Gr3-MB.

Implication of the Study’s Findings

The study’s findings have significant implications for the potential treatment of Gr3-MB and bring us closer to understanding the complex nature of brain cancer. The success of this research could provide hope for the future of treatment for this condition, which currently has a high risk of metastasis and leads to poor survival rates.

Conclusion

The discovery of a small population of stem-like cells is a significant step forward in understanding the development and growth of the most aggressive form of brain cancer in children. Eliminating the small population of cancer stem-like cells that sustain the tumor is an approach that is analogous to triggering the dissolution of an army by removing the leader, and has produced effective results in animal models. More research is needed, but this novel approach may lead to new ways to treat children with Gr3-MB, offering hope for patients and their families.

Keywords:

Group 3 medulloblastoma
stem-like cells
brain cancer
cancer stem cells
immunotherapy
tumor growth
metastasis
pediatric neuro-oncology

Originally Post From https://medicalxpress.com/news/2024-07-stem-cells-medulloblastoma-tumors-preclinical.html