生物
髓母细胞瘤
肿瘤微环境
肿瘤进展
神经发生
旁分泌信号
音猬因子
癌症研究
小胶质细胞
细胞生物学
神经科学
免疫学
癌症
信号转导
遗传学
受体
肿瘤细胞
炎症
作者
Maojin Yao,Patrick Ventura,Ying Jiang,Fausto J. Rodríguez,Lixin Wang,Justin C. Perry,Ying Yang,Kelsey Wahl,Rowena B. Crittenden,Mariko L. Bennett,Lin Qi,Congcong Gong,Xiao Nan Li,Ben A. Barres,Timothy P. Bender,Kodi S. Ravichandran,Kevin A. Janes,Charles G. Eberhart,Hui Zong
出处
期刊:Cell
[Elsevier]
日期:2020-02-01
卷期号:180 (3): 502-520.e19
被引量:100
标识
DOI:10.1016/j.cell.2019.12.024
摘要
The tumor microenvironment (TME) is critical for tumor progression. However, the establishment and function of the TME remain obscure because of its complex cellular composition. Using a mouse genetic system called mosaic analysis with double markers (MADMs), we delineated TME evolution at single-cell resolution in sonic hedgehog (SHH)-activated medulloblastomas that originate from unipotent granule neuron progenitors in the brain. First, we found that astrocytes within the TME (TuAstrocytes) were trans-differentiated from tumor granule neuron precursors (GNPs), which normally never differentiate into astrocytes. Second, we identified that TME-derived IGF1 promotes tumor progression. Third, we uncovered that insulin-like growth factor 1 (IGF1) is produced by tumor-associated microglia in response to interleukin-4 (IL-4) stimulation. Finally, we found that IL-4 is secreted by TuAstrocytes. Collectively, our studies reveal an evolutionary process that produces a multi-lateral network within the TME of medulloblastoma: a fraction of tumor cells trans-differentiate into TuAstrocytes, which, in turn, produce IL-4 that stimulates microglia to produce IGF1 to promote tumor progression.
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