Tracking cell invasion of human glioma cells and suppression by anti-matrix metalloproteinase agent in rodent brain-slice model.
Persistent expression of green fluorescent protein (GFP) in human malignant glioma cell clones (U87MG, U251MG, and U373MG) was established using the pEGFP-Cl vector. Tumor spheroid was implanted into the caudate nucleus-putamen of a severely compromised immunodeficient (SCID) mouse brain slice. To allow quantitative assessment of tumor cell invasion, the invasion area index was measured on days 1, 3, 5, and 7 by a fluorescence stereomicroscope and an image analyzer in the presence of varying concentrations of SI-27. In the control group (0 microg/ml), all glioma cell lines invaded in a fingerlike fashion, reaching the contralateral hemisphere via the corpus callosum. SI-27 at concentrations of 10, 50, or 100 microg/ml significantly suppressed the index on days 5 and 7 in a dose-dependent manner, whereas 1 microg/ml had no effect. Laser confocal microscopy indicated that the tumor cells penetrated through the brain slice. This model enabled unequivocal periodic tracking of individual invading tumor cells in the normal brain. The significant suppression of glioma cell invasion by SI-27 indicates that anti-matrix metalloproteinase (MMP) treatment may represent an important future therapeutic strategy for malignant cerebral neoplasms.
Yoshida
Daizo
D
Department of Neurosurgery, Nippon Medical School, 1-1-5 Sendagi Bunkyo-ku, Tokyo 113-8603, Japan. dyoshida@nms.ac.jp
Watanabe
Kunihiro
K
Noha
Masahiro
M
Takahashi
Hiroshi
H
Teramoto
Akira
A
Sugisaki
Yuichi
Y
D000818:Animals; D001921:Brain / Q000473:pathology*; D001932:Brain Neoplasms / Q000473:pathology*; D002460:Cell Line; D017690:Cell Transplantation; D002999:Clone Cells; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005434:Flow Cytometry; D005910:Glioma / Q000473:pathology*; D049452:Green Fluorescent Proteins; D006801:Humans; D066298:In Vitro Techniques; D008164:Luminescent Proteins; D061965:Matrix Metalloproteinase Inhibitors; D051379:Mice; D016513:Mice, SCID; D009361:Neoplasm Invasiveness / Q000473:pathology; D009368:Neoplasm Transplantation; D009842:Oligopeptides / Q000494:pharmacology*; D014162:Transfection; D014407:Tumor Cells, Cultured
D004791:Enzyme Inhibitors; D008164:Luminescent Proteins; D061965:Matrix Metalloproteinase Inhibitors; D009842:Oligopeptides; C421267:SI 27; D049452:Green Fluorescent Proteins