Astrocytes represent the most abundant glial cells in the brain, which are also present in tumor tissues of human and mouse MB. However, it was not known what functions astrocytes have in MB growth. In our previous studies, genetic ablation of astrocytes significantly inhibits MB progression in vivo, indicating that astrocytes play a critical role in supporting MB progression. Our studies further revealed that astrocytes support tumor cell proliferation through paracrine secretion of sonic hedgehog ligand. Consistent with the indispensable functions of astrocytes for tumor growth, tumor cells even can generate astrocytes by trans-differentiation to facilitate MB relapse. Trans-differentiation of tumor cells is driven by the BMP signaling. Tumor relapse occurs in approximately 30% of human MB, represents the most adverse prognostic factor in MB. Our studies demonstrate the important role of astrocytes in MB growth and relapse, and establish a promising approach to treat MB recurrence through interfering with tumor cell trans-differentiation.
Tumor cells generate astrocyte-like cells that contribute to SHH-driven medulloblastoma relapse
Guo, D.C., Wang, Y., Cheng, Y., Liao, S., Hu, J., Du, F., Xu, G., Liu, Y., Cai, K., Cheung, M., Wainwright, B.J., Lu, Q., Zhao, Y., Yang, Z.J. Journal of Experimental Medicine 218(9): e20202350 (2021) PMCID: PMC8282281
•Highlighed by Qadeer, Z., Weiss, W.A., A SHHecret target of relapsed medulloblastoma: Astrocytes. J. Experimental Medicine, 218 (9), 2021. PMID: 34398189
Astrocytes promote medulloblastoma progression through hedgehog secretion
Liu, Y., Yuelling, L.W., Wang, Y., Du, F., Gordon, R.E., O'Brien, J., Ng, J.M.Y., Robins, S., Lee, E.H., Liu, H., Curran, T., Yang, Z.J. Cancer Research 77(23):6692-6703 (2017) PMCID: PMC5759326 PDF