Spontaneous regression of experimental gliomas--an immunohistochemical and MRI study of the C6 glioma spheroid implantation model.
OBJECTIVE
The orthotopic C6 glioma spheroid implantation model has been used to examine factors of neoangiogenesis, growth factor release, and protease expression as well the effect of antitumor agents. The present study systematically investigates the long-term course of orthotopically implanted C6 spheroid gliomas.


METHODS
Reaggregated C6 spheroid tumors were implanted into the forebrain of 48 male Sprague-Dawley rats (32 immunocompetent, 16 thymectomized). The animals were examined by MRI at postoperative day (POD) 7, 14, 21, 28, 32, 45, 60, and 70. The MRI protocol included a T2-w and T1-w SE sequence before and after application of contrast medium and a CISS 3D sequence for volumetry. A total of six animals were selected after each MR exam from both groups and sacrificed for HE light microscopy and CD8+ T-lymphocyte, ED1+ macrophage, CD31+ endothelial cell immunohistochemistry.


RESULTS
The tumors progressed to reach a maximum volume on day 28: 0.23 +/- 0.05 ml in the thymectomized and 0.16 +/- 0.021 ml in the immunocompetent group. Tumors then consistently regressed to vanish completely by POD 70. The influx of cytotoxic CD8+ T-lymphocytes correlated with tumor progression and the tumors reached a larger size in the thymectomized group. However, the time course of tumor regression was the same for both groups.


CONCLUSIONS
The present data suggest that the orthotopic C6 glioma implanted into Sprague-Dawley rats will progress within a time span of approximately 4 weeks and can then retrogress again spontaneously. This finding has to be taken into account when deciding on a study protocol and the appropriate animal model. The C6 glioma model may be suitable to study the cell biological steps involved in the phenomenon of spontaneous tumor regression.
Vince
Giles H
GH
Department of Neurosurgery, University of Wuerzburg, Germany. vince.g@nch.uni-wuerzburg.de
Bendszus
Martin
M
Schweitzer
Tilmann
T
Goldbrunner
Roland H
RH
Hildebrandt
Sabine
S
Tilgner
Johannes
J
Klein
Rüdiger
R
Solymosi
Laszlo
L
Christian Tonn
Jörg
J
Roosen
Klaus
K
D000818:Animals; D001932:Brain Neoplasms / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D045744:Cell Line, Tumor / Q000637:transplantation; D017690:Cell Transplantation / Q000379:methods; D053331:Ectodysplasins; D005910:Glioma / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D009365:Neoplasm Regression, Spontaneous; D009368:Neoplasm Transplantation / Q000379:methods; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D016548:Prosencephalon / Q000276:immunology / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018874:Spheroids, Cellular
D053331:Ectodysplasins; D008565:Membrane Proteins; D019408:Platelet Endothelial Cell Adhesion Molecule-1