Fox Chase Researchers Find That Astrocytes Generated by Tumor Cells Contribute to SHH-Driven Medulloblastoma Relapse

Researchers at Fox Chase Cancer Center have recently shown that sonic hedgehog-driven (SHH) medulloblastoma relapse may be prevented by targeting the transdifferentiation—a cell's ability to convert from one type of cell to another—of astrocytes.

Medulloblastoma is the most common malignant pediatric brain tumor. It forms at the back of the brain and can quickly spread to other areas of the brain through cerebrospinal fluid. Medulloblastoma accounts for about 20% of all childhood brain tumors. Although aggressive treatment has helped improve outcomes, an estimated 20% to 30% of patients relapse.

"It has already been found that tumor-supporting cells are very important for tumor growth, either in primary tumors or relapsed tumors. Right now, there is no good way to specifically target those tumor microenvironments," said Zeng-jie Yang, MD, PhD, lead author on the study.

"For medulloblastoma, it has been well established that astrocytes are very important for tumor growth or relapse, but so far there has been no good way to target those astrocytes," added Yang, an associate professor in the Cancer Signaling and Epigenetics Research Program at Fox Chase.

Astrocytes, a type of glial cell in the nervous system, contribute significantly to the progression of medulloblastoma by secreting SHH. According to the study, which was done in a mouse model, these astrocytes form as a result of transdifferentiation of tumor cells in relapsed medulloblastoma..

"This transdifferentiation process is mediated by a pathway called a bone morphogenetic protein, or BMP, pathway. This pathway induces phosphorylation, which is very important for a transcription factor called Sox9," said Yang. A transcription factor is a protein that plays a vital role in converting or transcribing DNA into RNA.

Yang said that based on the findings from this study, researchers were able to use a BMP pathway inhibitor drug and ultimately show that using them may prevent medulloblastoma cell transdifferentiation into astrocytes to suppress tumor relapse.

"The main point of our study suggests that tumor cells have the capacity to generate other tumor cells as well as supporting cells—non-tumor cells. In light of this finding, we will continue to work on the construction of the tumor microenvironment in metastatic tumors," said Yang, who worked on the study with other research centers in the United States, as well as in Australia and China.

The study, "Tumor Cells Generate Astrocyte-Like Cells That Contribute to SHH-Driven Medulloblastoma Relapse," was published in the Journal of Experimental Medicine.

About Fox Chase Cancer Center

The Hospital of Fox Chase Cancer Center and its affiliates (collectively "Fox Chase Cancer Center"), a member of the Temple University Health System, is one of the leading cancer research and treatment centers in the United States. Founded in 1904 in Philadelphia as one of the nation's first cancer hospitals, Fox Chase was also among the first institutions to be designated a National Cancer Institute Comprehensive Cancer Center in 1974. Fox Chase researchers have won the highest awards in their fields, including two Nobel Prizes. Fox Chase physicians are also routinely recognized in national rankings, and the Center's nursing program has received the Magnet recognition for excellence five consecutive times. Today, Fox Chase conducts a broad array of nationally competitive basic, translational, and clinical research, with special programs in cancer prevention, detection, survivorship and community outreach. It is the policy of Fox Chase Cancer Center, that no one shall be excluded from or denied the benefits of or participation in the delivery of quality medical care on the basis of race, ethnicity, religion, sexual orientation, gender, gender identity/expression, disability, age, ancestry, color, national origin, physical ability, level of education, or source of payment.