169 NEURAL STEM CELLS SUPPRESS PROSTATE CANCER GROWTH BY BLOCKING PATHOLOGIC ANGIOGENESIS IN VIVO

You have accessJournal of UrologyStem Cell Research1 Apr 2011169 NEURAL STEM CELLS SUPPRESS PROSTATE CANCER GROWTH BY BLOCKING PATHOLOGIC ANGIOGENESIS IN VIVO Charles Brendler, Philip Fitchev, Margo Quinn, Lijun Huang, Mona Cornwell, Jennifer Doll, Beth Plunkett, and Susan Crawford Charles BrendlerCharles Brendler Evanston, IL More articles by this author , Philip FitchevPhilip Fitchev Evanston, IL More articles by this author , Margo QuinnMargo Quinn Evanston, IL More articles by this author , Lijun HuangLijun Huang Evanston, IL More articles by this author , Mona CornwellMona Cornwell Evanston, IL More articles by this author , Jennifer DollJennifer Doll Evanston, IL More articles by this author , Beth PlunkettBeth Plunkett Evanston, IL More articles by this author , and Susan CrawfordSusan Crawford Evanston, IL More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.238AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Perineural invasion in prostate cancer is associated with more aggressive biological behavior; however, the mechanisms underlying this association are unclear. Interestingly, factors known to suppress angiogenesis such as pigment epithelium-derived factor (PEDF) are potent survival factors for cells of neural origin. Higher grade tumors also have a lower nerve density, suggesting that vascular-neural crosstalk is critical in modulating the tumor microenvironment. We postulated that nerves provide a natural barrier to tumor growth by secreting inhibitors of angiogenesis into the stroma and that these same factors, in turn, promote nerve survival. METHODS Secretions collected from murine peripheral nerves, Schwann cells, and neural stem cells were tested for the presence of angiogenic factors by Western blot and analyzed for angiogenic activity in a microvascular endothelial cell migration assay. VEGF-enriched hydron pellets were implanted adjacent to intact or damaged sciatic nerves and microvascular density was assessed. Additionally, PC-3 prostate cancer cells were grown in a nude mouse model and the subsequent tumors were treated with neural stem cells or PBS as a control. Tumor tissue was analyzed for volume, angiogenic activity, and tumor morphology. RESULTS We found that neural cells secrete a cocktail of biologically active inhibitors of angiogenesis including PEDF, angiostatin, and thrombospondin-1. These angiogenic inhibitors from intact nerves can also block VEGF-induced neovascularization. Moreover, treatment of PC-3 prostate cancer xenografts with neural stem cells significantly decreased angiogenesis and reduced mitosis and tumor volume. CONCLUSIONS These data suggest that perineural invasion damages an important intrinsic stromal source of factors that block angiogenesis. Therapeutic delivery of stem cells as a renewable source of anti-angiogenic mediators may reduce prostate cancer tumor progression. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e71 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Charles Brendler Evanston, IL More articles by this author Philip Fitchev Evanston, IL More articles by this author Margo Quinn Evanston, IL More articles by this author Lijun Huang Evanston, IL More articles by this author Mona Cornwell Evanston, IL More articles by this author Jennifer Doll Evanston, IL More articles by this author Beth Plunkett Evanston, IL More articles by this author Susan Crawford Evanston, IL More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...