Astrocytes Promote Medulloblastoma Progression through Hedgehog Secretion.

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.

• Authors: Yongqiang Liu, Larra W Yuelling, Yuan Wang, Fang Du, Renata E Gordon, Jenny A O'Brien, Jessica M Y Ng, Shannon Robins, Eric H Lee, Hailong Liu, Tom Curran, Zeng-Jie Yang
• Journal: Cancer research (Cancer Res) Vol. 77 Issue 23 Pg. 6692-6703 (12 01 2017) ISSN: 1538-7445 [Electronic] United States
• PMID: 28986380 (Publication Type: Journal Article)
• Copyright: ©2017 American Association for Cancer Research.

Chemical References

• Gli1 protein, mouse
• Hedgehog Proteins
• Nes protein, mouse
• Nestin
• Patched-1 Receptor
• Ptch1 protein, mouse
• Shh protein, mouse
• Smo protein, mouse
• Smoothened Receptor
• Zinc Finger Protein GLI1

Topics

• Animals
• Astrocytes (metabolism)
• Carcinogenesis (pathology)
• Cell Proliferation (physiology)
• Cells, Cultured
• Cerebellar Neoplasms (pathology)
• Hedgehog Proteins (metabolism)
• Medulloblastoma (pathology)
• Mice
• Mice, Transgenic
• Nestin (biosynthesis)
• Patched-1 Receptor (metabolism)
• Smoothened Receptor (metabolism)
• Tumor Microenvironment (physiology)
• Zinc Finger Protein GLI1 (metabolism)