Instructive cross-talk between neural progenitor cells and gliomas.
Gliomas are the most common primary brain tumors and offer a poor prognosis in patients because of their infiltrative and treatment-resistant nature. The median survival time after diagnosis is approximately 11-12 months. There is a strong need for novel treatment modalities in targeting gliomas, and recent advances use neural progenitor cells as delivery systems for different therapeutic strategies. In this study, we show that rat embryonic neural progenitor cell (NPC) lines, transplanted at a distant site from a 3-day-preestablished glioma in the striatum, were able to migrate toward and colocalize with tumor isles without general spread into the brain parenchyma. Upon encounter with tumor, neural progenitor cells changed phenotype and became vimentin positive. These results demonstrate that transplanted neural progenitor cells respond to queues from a tumor and home to and exert an antitumor effect on the preestablished glioma, significantly decreasing the tumor volume with approximately 67% compared with control tumors after 1-2 weeks. Moreover, these early effects could be translated into increased survival times of animals treated with neural progenitor cell grafts 3 days after intrastriatal tumor inoculation. In contrast, there was no activation or migration of endogenous subventricular zone (SVZ) neuroblasts in response to an intrastriatal syngeneic tumor. In conclusion, NPC possess the ability to influence tumor growth as well as respond to queues from the tumor or tumor microenvironment, demonstrating a cross-talk between the cells.
Staflin
Karin
K
Wallenberg Neuroscience Center, Department of Experimental Medical Science, Lund University, Lund, Sweden.
Lindvall
Magnus
M
Zuchner
Thole
T
Lundberg
Cecilia
C
D000818:Animals; D001932:Brain Neoplasms / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D002450:Cell Communication; D045744:Cell Line, Tumor; D002465:Cell Movement; D002470:Cell Survival; D003342:Corpus Striatum; D005910:Glioma / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D009474:Neurons / Q000166:cytology*; D010641:Phenotype; D051381:Rats; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism / Q000502:physiology*; D014746:Vimentin / Q000378:metabolism
D014746:Vimentin