PEX-producing human neural stem cells inhibit tumor growth in a mouse glioma model

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Kim, Seung-Ki; Cargioli, Theresa G; Machluf, Marcelle; Yang, Wendy; Sun, Yanping; Al-Hashem, Ruqayyah; Kim, Seung U; Black, Peter M; Carroll, Rona S
Issue Date
American Association for Cancer Research
Clin Cancer Res. 2005 Aug 15;11(16):5965-70.
AnimalsBrain/cytology/embryologyCell LineCell Line, TumorCell MovementCell ProliferationCell SurvivalCoculture TechniquesGlioma/blood supply/pathology/*prevention & controlHumansMatrix Metalloproteinase 2/genetics/*metabolismMiceMice, NudeNeovascularization, Pathologic/pathology/prevention & controlPeptide Fragments/geneticsStem Cell TransplantationStem Cells/cytology/*metabolismTransfectionXenograft Model Antitumor Assays/*methods
A unique characteristic of neural stem cells is their capacity to track glioma cells that have migrated away from the main tumor mass into the normal brain parenchyma. PEX, a naturally occurring fragment of human metalloproteinase-2, acts as an inhibitor of glioma and endothelial cell proliferation, migration, and angiogenesis. In the present study, we evaluated the antitumor activity of PEX-producing human neural stem cells against malignant glioma. The HB1.F3 cell line (immortalized human neural stem cell) was transfected by a pTracer vector with PEX. The retention of the antiproliferative activity and migratory ability of PEX-producing HB1.F3 cells (HB1.F3-PEX) was confirmed in vitro. For the in vivo studies, DiI-labeled HB1.F3-PEX cells were stereotactically injected into established glioma tumor in nude mice. Tumor size was subsequently measured by magnetic resonance imaging and at the termination of the studies by histologic analysis including tumor volume, microvessel density, proliferation, and apoptosis rate. Histologic analysis showed that DiI-labeled HB1.F3-PEX cells migrate at the tumor boundary and cause a 90% reduction of tumor volume (P < 0.03). This reduction in tumor volume in animals treated with HB1.F3-PEX was associated with a significant decrease in angiogenesis (44.8%, P < 0.03) and proliferation (23.6%, P < 0.03). These results support the use of neural stem cells as delivery vehicle for targeting therapeutic genes against human glioma.
1078-0432 (Print)
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College of Medicine/School of Medicine (의과대학/대학원)Neurosurgery (신경외과학전공)Journal Papers (저널논문_신경외과학전공)
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