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Mol Med Rep. 2015 Nov;12(5):6435-44. doi: 10.3892/mmr.2015.4228. Epub 2015 Aug 18.

Characterization of highly proliferative secondary tumor clusters along host blood vessels in malignant glioma.

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Department of Neurosurgery, Chang‑Gung Memorial Hospital, Chiayi 613, Taiwan, R.O.C.
Department of Radiation Oncology, Chang‑Gung Memorial Hospital, Chiayi 613, Taiwan, R.O.C.
Graduate Institute of Clinical Medical Sciences, Chiayi Branch, College of Medicine, Chang‑Gung University, Chiayi 613, Taiwan, R.O.C.


The aim of the present study was to investigate the extensive invasion of tumor cells into normal brain tissue, a life‑threatening feature of malignant gliomas. How invasive tumor cells migrate into normal brain tissue and form a secondary tumor structure remains to be elucidated. In the present study, the morphological and phenotypic changes of glioma cells during invasion in a C6 glioma model were investigated. C6 glioma cells were stereotactically injected into the right putamen region of adult Sprague‑Dawley rats. The brain tissue sections were then subjected to hematoxylin and eosin, immunohistochemical or immunofluorescent staining. High magnification views of the tissue sections revealed that C6 cells formed tumor spheroids following implantation and marked invasion was observed shortly after spheroid formation. In the later stages of invasion, certain tumor cells invaded the perivascular space and formed small tumor clusters. These small tumor clusters exhibited certain common features, including tumor cell multilayers surrounding an arteriole, which occurred up to several millimeters away from the primary tumor mass; a high proliferation rate; and similar gene expression profiles to the primary tumor. In conclusion, the present study revealed that invading tumor cells are capable of forming highly proliferative cell clusters along arterioles near the tumor margin, which may be a possible cause of the recurrence of malignant glioma.

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