Transplanted glioma cells migrate and proliferate on host brain vasculature: a dynamic analysis.
Glioma cells have a remarkable capacity to infiltrate the brain and migrate long distances from the tumor, making complete surgical resection impossible. Yet, little is known about how glioma cells interact with the complex microenvironment of the brain. To investigate the patterns and dynamics of glioma cell infiltration and migration, we stereotactically injected eGFP and DsRed-2 labeled rat C6 glioma cells into neonatal rat forebrains and used time-lapse microscopy to observe glioma cell migration and proliferation in slice cultures generated from these brains. In this model, glioma cells extensively infiltrated the brain by migrating along the abluminal surface of blood vessels. Glioma cells intercalated their processes between the endothelial cells and the perivascular astrocyte end feet, but did not invade into the blood vessel lumen. Dynamic analysis revealed notable similarities between the migratory behavior of glioma cells and that previously observed for glial progenitor cells. Glioma cells had a characteristic leading process and migrated in a saltatory fashion, with bursts of migration separated by periods of immobility, and maximum speeds of over 100 microm/h. Migrating glioma cells proliferated en route, pausing for as short as an hour to divide before the daughter cells resumed migrating. Remarkably, the majority of glioma cell divisions took place at or near vascular branch points, suggesting that mitosis is triggered by local environmental cues. This study provides the first dynamic analysis of glioma cell infiltration in living brain tissue and reveals that the migration and proliferation of transplanted glioma cells is directed by interactions with host brain vasculature.
Farin
Azadeh
A
Department Neurological Surgery, Columbia University, College of Physicians and Surgeons, New York, NY 10032, USA.
Suzuki
Satoshi O
SO
Weiker
Michael
M
Goldman
James E
JE
Bruce
Jeffrey N
JN
Canoll
Peter
P
D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000166:cytology / Q000502:physiology; D001808:Blood Vessels / Q000473:pathology / Q000503:physiopathology*; D001812:Blood-Brain Barrier / Q000473:pathology / Q000503:physiopathology; D001921:Brain / Q000098:blood supply* / Q000473:pathology / Q000503:physiopathology*; D001932:Brain Neoplasms / Q000503:physiopathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D049109:Cell Proliferation; D042783:Endothelial Cells / Q000166:cytology / Q000502:physiology; D005910:Glioma / Q000503:physiopathology*; D049452:Green Fluorescent Proteins; D008164:Luminescent Proteins; D009361:Neoplasm Invasiveness / Q000503:physiopathology*; D009924:Organ Culture Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D016378:Tissue Transplantation / Q000379:methods
D008164:Luminescent Proteins; C485184:enhanced green fluorescent protein; C413663:fluorescent protein 583; D049452:Green Fluorescent Proteins