Article
Spontaneous regression of experimental gliomas – An MRI and immunohistochemical study of the C6 glioma spheroid implantation model
Spontane Regression experimenteller Gliome - eine MR und immunhistochemische Studie des C6-Sphaeroid-Implantationsmodells
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Published: | April 23, 2004 |
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Outline
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Objective
The C6 glioma spheroid model is extensively used to study the growth kinetics and mechanisms of neoangiogenesis as well as the expression of growth factors and receptors involved in the progression of an astrocytic tumour. The present investigation demonstrates the natural course of C6 tumour development and offers a possible explanation for the observation that tumour cell spheroids display pronounced spontaneous regressive alterations to the point of complete remission.
Methods
Spheroids of C6 glioma cell lines were implanted into the brain of 32 immunocompetent and 16 thymectomized Sprague-Dawley rats. MRI scans were performed at regular intervals and used for volumetric analysis. The rats were sacrificed at defined points in time. Frozen sections were prepared and stained for macrophages, CD8+ T-lymphocytes and NK cells. Additional PCNA, CD31 and HE histochemistry was performed.
Results
MRI demonstrated tumour growth and progression after implantation up until day 28. Tumour and oedema mass effect peaked between day 21 and 36. From day 21 on necrosis developed. Remarkably, in both groups tumours then regressed to disappear completely by day 70. Immunodeficient rats developed larger tumours. CD8+ lymphocytes and ED-1+ macrophages influxed in both groups until day 28 and then returned to baseline counts. NK-cells increased continuously in both groups.
Conclusions
Our results confirm the C6 glioma model best mimics the cell biological stages of early glioma progression. The present data suggest, however, that the implanted C6 glioma will progress within a time span of approximately 4 weeks and can then retrogress spontaneously to the point of complete remission. Regression appears to be the result of an immunological host response with an influx of macrophages and NK-cells. These findings have to be taken into account when employing this well-established study model.