Astrocytes Promote Medulloblastoma Progression through Hedgehog Secretion.
Astrocytes Promote Medulloblastoma Progression through Hedgehog Secretion.
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星形胶质细胞通过刺猬蛋白分泌促进髓母细胞瘤进展
DOI：
10.1158/0008-5472.can-17-1463
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发表时间：
2017-12-01
期刊：
影响因子：
11.2
通讯作者：
Yang ZJ
中科院分区：
文献类型：
--
作者：
Liu Y;Yuelling LW;Wang Y;Du F;Gordon RE;O'Brien JA;Ng JMY;Robins S;Lee EH;Liu H;Curran T;Yang ZJ
星形胶质细胞是大脑中最丰富的神经胶质细胞类型，在支持神经元发育和大脑功能方面发挥着关键作用。虽然星形胶质细胞经常在包括髓母细胞瘤（MB）在内的脑肿瘤中被发现，但它们在肿瘤发生中的功能尚不清楚。在这里，我们证明星形胶质细胞是 MB 肿瘤微环境的重要组成部分。肿瘤相关星形胶质细胞 (TAA) 分泌配体声波刺猬 (Shh)，尽管缺乏其主要受体 Patched-1 (Ptch1)，但它是维持 MB 细胞增殖所必需的。 Shh 通过依赖 Smoothened、不依赖 Gli1 的机制驱动 MB 细胞中 Nestin 的表达。 TAA 的消融显着抑制了巢蛋白的表达并阻止了肿瘤的生长。这些发现证明星形胶质细胞在 MB 肿瘤发生中发挥着不可或缺的作用，并揭示了一种参与 MB 进展的新型 Ptch1 独立 Shh 通路。
Astrocytes, the most abundant type of glial cells in the brain, play critical roles in supporting neuronal development and brain function. While 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) secreted the ligand sonic hedgehog (Shh), which is required for maintaining MB cell proliferation despite the absence of its primary receptor Patched-1 (Ptch1). Shh drove expression of Nestin in MB cells through a Smoothened-dependent, Gli1-independent mechanism. Ablation of TAA dramatically suppressed Nestin expression and blocked 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.