Abstract：
:Astrocytes, the most abundant type of glial cells in the brain, play critical roles in supporting neuronal development and brain function. Although astrocytes have been frequently detected in brain tumors, including medulloblastoma (MB), their functions in tumorigenesis are not clear. Here, we demonstrate that astrocytes are essential components of the MB tumor microenvironment. Tumor-associated astrocytes (TAA) secrete the ligand sonic hedgehog (Shh), which is required for maintaining MB cell proliferation despite the absence of its primary receptor Patched-1 (Ptch1). Shh drives expression of Nestin in MB cells through a smoothened-dependent, but Gli1-independent mechanism. Ablation of TAA dramatically suppresses Nestin expression and blocks tumor growth. These findings demonstrate an indispensable role for astrocytes in MB tumorigenesis and reveal a novel Ptch1-independent Shh pathway involved in MB progression. Cancer Res; 77(23); 6692-703. ©2017 AACR.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Liu Y,Yuelling LW,Wang Y,Du F,Gordon RE,O'Brien JA,Ng JMY,Robins S,Lee EH,Liu H,Curran T,Yang ZJdoi
10.1158/0008-5472.CAN-17-1463subject
Has Abstractpub_date
2017-12-01 00:00:00pages
6692-6703issue
23eissn
0008-5472issn
1538-7445pii
0008-5472.CAN-17-1463journal_volume
77pub_type
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