astrocyte-specific expression patterns associated with the pdgf-induced glioma microenvironmentastrocyte-specific表达模式与神经胶质瘤pdgf-induced微环境有关.pdfVIP

Astrocyte-Specific Expression Patterns Associated with the PDGF-Induced Glioma Microenvironment Amanda M. Katz1,2,3, Nduka M. Amankulor2,3,4, Ken Pitter1,2,3, Karim Helmy2,3, Massimo Squatrito2,3, Eric C. Holland2,3,4* 1 Biochemistry, Cell, and Molecular Biology Program, Weill Medical College of Cornell University, New York, New York, United States of America, 2 Department of Cancer Biology and Genetics, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America, 3 Brain Tumor Center, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America, 4 Departments of Neurosurgery, Neurology and Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America Abstract Background: The tumor microenvironment contains normal, non-neoplastic cells that may contribute to tumor growth and maintenance. Within PDGF-driven murine gliomas, tumor-associated astrocytes (TAAs) are a large component of the tumor microenvironment. The function of non-neoplastic astrocytes in the glioma microenvironment has not been fully elucidated; moreover, the differences between these astrocytes and normal astrocytes are unknown. We therefore sought to identify genes and pathways that are increased in TAAs relative to normal astrocytes and also to determine whether expression of these genes correlates with glioma behavior. Methodology/Principal Findings: We compared the gene expression profiles of TAAs to normal astrocytes and found the Antigen Presentation Pathway to be significantly increased in TAAs. We then identified a gene signature for glioblastoma (GBM) TAAs and validated the expression of some of those genes within the tumor. We also show that TAAs are derived from the non-tumor, stromal environment, in contrast to the Olig2+ tumor cells that constitute the neoplastic elements in our model. F