Authors: Stephen M Selkirk Jay Morrow Tara A Barone Alan Hoffer Jeffrey Lock Anne DeChant Saisho Mangla Robert J Plunkett Robert H Miller
Publish Date: 2007/10/11
Volume: 86, Issue: 3, Pages: 285-296
Abstract
Osteopontin OPN is a pleotrophic molecule that has been associated with multiple disorders of the central nervous system CNS Its roles in CNS malignancy are unclear but suggest that higher levels of OPN expression correlate with increased tumor grade and increased migratory capacity of tumor cells In this study OPN cDNA was cloned into a retroviral vector and used to infect F98 Fischer ratderived glioma cells and U87 humanderived glioblastoma multiforme GBM cells in vitro Cells expressing high levels of OPN migrated less distance than control cells in vitro This effect was not RGD mediated but was reversed in the presence of cJun Nterminal kinase JNK inhibitor suggesting that JNK1 is an essential component of a negative feedback loop affecting OPN activated signaling cascades Implantation of tumor cells expressing high levels of OPN into adult Fischer rats and nude rats resulted in morphologically distinct tumors and prolonged host survival relative to controls We propose that local produced high level OPN expression limits the malignant character of glioma cells and that the downstream mechanisms involved represent pathways that may have therapeutic value in the treatment of human CNS malignancyThis research was supported by NIH grants NS3667408 NS3080011 and CA10373602 to RHM F98 and U87 cells were provided by Dr Steven M Greenberg Roswell Park Cancer Institute We would like to thank Anita Zaremba for technical assistance with slice culture preparation
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