the p75 neurotrophin receptor is a central regulator of glioma invasion我生成受体是神经胶质瘤的中央监管机构入侵.pdfVIP

PLoS BIOLOGY The p75 Neurotrophin Receptor Is a Central Regulator of Glioma Invasion Angela L. M. Johnston1,2,3, Xueqing Lun1,2,3,4,5, Jennifer J. Rahn1,2,3,4, Abdelhamid Liacini1,2,3,4,5, Limei Wang1,2,3,4,5, Mark G. Hamilton3,5 2,3,4,5 6 1,2,3,4 1,2,3,4,5* , Ian F. Parney , Barbara L. Hempstead , Stephen M. Robbins , Peter A. Forsyth , 2,3,4* Donna L. Senger 1 Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, Alberta, Canada, 2 Southern Alberta Cancer Research Institute, Calgary, Alberta, Canada, 3 Clark H. Smith Integrative Brain Tumour Research Center, Calgary, Alberta, Canada, 4 Department of Oncology, University of Calgary, Calgary, Alberta, Canada, 5 Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada, 6 Division of Hematology, Cornell University Medical College, New York, New York, United States of America The invasive nature of cancers in general, and malignant gliomas in particular, is a major clinical problem rendering tumors incurable by conventional therapies. Using a novel invasive glioma mouse model established by serial in vivo selection, we identified the p75 neurotrophin receptor (p75NTR) as a critical regulator of glioma invasion. Through a series of functional, biochemical, and clinical studies, we found that p75NTR dramatically enhanced migration and invasion of genetically distinct glioma and frequently exhibited robust expression in highly invasive glioblastoma patient specimens. Moreover, we found that p75NTR-mediated invasion was neurotrophin dependent, resulting in the activat