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NF Center Researchers Identify a New Growth Regulatory Circuit Critical for Malignant Glioma Survival

Glioblastoma (GBM) are the most malignant brain tumor in adults, with over 13,000 people in the United States dying from these cancers each year. GBM tumors are genetically different from each other, and one class of these tumors is characterized by neurofibromatosis type 1 (NF1) mutation or loss of NF1 gene expression (“mesenchymal GBM” tumors).

In order to understand how tumor growth in this class of GBM is controlled, Dr. Yuan Pan and her colleagues at the Washington University NF Center leveraged previous findings made in Nf1 low-grade brain tumor (gliomas) to discover that a small protein, called Ccl5, is critical for GBM growth.

These earlier studies showed that Nf1 mouse optic gliomas require that immune system cells supply Ccl5 to maintain brain tumor growth. Dr. Pan wondered whether this same protein might be responsible for mesenchymal GBM growth.

In the current study, she showed that CCL5 is highly expressed by mesenchymal GBM cells, but not by other GBM subtypes. Next, she demonstrated that Ccl5 prevents the tumor cells from dying, such that reducing Ccl5 expression in mouse mesenchymal GBM cells improved overall mouse survival. Finally, she determined precisely how Ccl5 controls GBM growth, suggesting new treatment strategies for these deadly brain cancers.

This study was published in the journal, Oncotarget.

Pan Y, Smithson LJ, Ma Y, Hambardzumyan D, Gutmann DH. Ccl5 establishes an autocrine high-grade glioma growth regulatory circuit critical for mesenchymal glioblastoma survival. Oncotarget. 2017 Mar 23. doi: 10.18632/oncotarget.16516. [Epub ahead of print]