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

Abstract

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.

Embedding MRI information into MRSI data source extraction improves brain tumour delineation in animal models

“…In this particular murine model, and according to the veterinary pathologist, PI > 30% would correspond to a safe threshold for identifying the solid tumour region, whereas a PI ≤ 5% would correspond to definitely non-tumour (excluding reactive gliosis and other phenomena). This is in agreement with other studies with murine glioma, in which a PI of 23.9% was found in tumour core, and 9.6% in tumour periphery [31].…”

Stoichioproteomics reveal oxygen usage bias, key proteins and pathways in glioma

“…Glioma is the most popular primary malignant tumor in neurosurgery [1], and its five-year survival rate is low, less than 10% [2]. As having been reported earlier [3], malignant glioma cells can extensively invade normal brain tissue, and form highly proliferative glioma cell clusters [4]. Moreover, the high infiltration of glioma is one of its features, which makes it extremely difficult to cure completely [5].…”

Cell Subpopulations Overexpressing p75NTR Have Tumor-initiating Properties in the C6 Glioma Cell Line

“…C6p75+ and C6p75+++ cells were used for tumorigenic experiments. A cell suspension (100 μl) was intracranially injected into four-week-old Sprague Dawley rats into their right hemisphere using a 100 μl microsyringe, similarly to the previously described method (35). In the present study, the injected cell numbers were 1×10 3 and 1×10 5 .…”

“…Western blotting. Western blotting was performed as previous studies (32,35). Cells were lysed with lysis buffer [1% Triton X-100, 50 mM of Tris(PH 7.5), 10 mM EDTA, and protease inhibitor cocktail (Roche, Indianapolis, IN, USA)].…”