Histological characteristics and markers of proliferation and differentiation in rat brain with experimental glioma (original) (raw)
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Rat C6 glioma as experimental model system for the study of glioblastoma growth and invasion
Cell and Tissue Research, 2002
Infiltration of the central nervous system by neoplastic cells in patients with glioblastoma multiforme (GBM) leads to neurological dysfunction and eventually to death. The elucidation of the mechanisms underlying the aggressive nature of GBM aims at improving radio-, chemo-and gene therapy. This review is focused on the use of rat C6 glioma as an experimental model system for GBM and provides an overview of the experimental data published in the literature using this cell line in elucidating the mechanism of tumor growth, angiogenesis and invasion, and in the design and evaluation of anticancer therapies. Understanding the stages of malignant brain tumor progression requires a series of experimental approaches with a varying degree of complexity. Implantation of malignant cells into animal brain tissue closely resembles in vivo tumor growth and has the advantage over simplified models that inflammatory and vascular mechanisms are activated. However, the complexity of these models makes it difficult to identify the individual processes involved in sustained tumor growth, angiogenesis and invasion. In cell culture models, the effect of growth factors, extracellular matrix components, proteases and adhesion molecules can be investigated. The secretion of tumor-derived factors into the medium can also be analyzed when simplified models are used. This review is a compilation of experimental data focused on the characterization of tumor-related processes and on the evaluation of new therapies for the treatment of malignant glial neoplasms using rat C6 glioma as a model system.
2005
Glial tumors are the largest group of central nervous system tumors and glioblastoma multiforme is the most common form. Glioblastomas are anaplastic forms of gliomas. Their high incidence and malignity have led researchers to work hard to better understand and treat these tumors. It is now known that genetic factors play a role in glioma etiopathogenesis. Of the differences in genetic built, two attract the most attention: oncogenes that lead to cell division and the occurrence of cells that have lost tumor suppressor genes. After realizing that the evolution of surgery and radiotherapy would have no significant value for malignant brain tumors, the trial of potential chemotherapeutic, genetic and immunologic therapy methods in an appropriate experimental glioma model has gained in importance. The C6 rat glioma model is used in these studies because of its similarity to the human glioblastoma. In this study, we used the C6 rat glioma model which has glioblastoma-like effects and tr...
Isolation and Characterization of Human Malignant Glioma Cells from Histologically Normal Brain
Journal of Neuro-Ophthalmology, 1997
ALIGNANT gliomas pose a formidable therapeutic challenge because of their invasive growth characteristics. Glioma cells that have infiltrated beyond gross tumor into histologically normal brain cannot be completely removed surgically; they are protected by an intact blood-brain barrier and do not appear to enter mitosis, thus making radiotherapy and chemotherapy less effective. Malignant glioma cells invade beyond abnormalities detected with computerized tomography and magnetic resonance (MR) imaging; 7,8,23 they often invade the brain more than 2 cm beyond the gross tumor, 7 are not usually found within the confines of a single carotid artery or vertebral artery distribution, 7 and are shown at autopsy to have extended farther than predicted antemortem. 7,15,20,21,31,32,35 However, in previous studies determination of the extent of tumor cell invasion relied on the identification of tumor cells in surgical or autopsy specimens using various standard staining techniques. Until now efforts have not been made to initiate tumor cells from histologically normal brain in culture to document their presence and to characterize these important cells biologically.
Bulletin of Experimental Biology and Medicine, 2010
In experiments on Wistar rats with experimental C6 glioma, the immunohistochemical features of the astroglial reaction over 30 days after implantation were characterized. The formation of a glial border consisting of GFAP-positive reactive astrocytes at the periphery of C6 glioma was observed on postimplantation day 3 and until the death of the experimental animals. Reactive astrocytes encompassed not only the primary gliomal focus, but all tumor invasion foci. Quantitative assessment of astroglial reaction around glioma was carried out with immunofl uorescent assay of glial fi brillary acidic protein (GFAP) on cerebral sections. The size of glioma and necrotic foci were analyzed morphometrically in parallel with enzyme immunoassay of serum GFAP. A correlation between morphometric indices of glioma and serum level of GFAP was found. It was concluded that serum concentration of GFAP correlated with the size of intracranial glioma, necrotic foci, and most strongly with the degree of reactive astrogliosis. Monitoring of the level of serum GFAP can serve as an additional diagnostic index reporting the state of intracranial glioma.
Modeling and immunohistochemical analysis of C6 glioma In Vivo
Bulletin of Experimental Biology and Medicine, 2007
A reproducible in vivo model of C6 glioma was developed in Wistar rats. Analysis of histological preparations showed similar morphology of rat C6 glioma and human glioblastoma. The formation of a glial border at the periphery of the glioma, consisting of GFAP-positive reactive astrocytes, was shown by the immunohistochemical method. The border appeared on day 8 after implantation, astrogliosis was observed until animal death (day 28). Reactive astrocytes with branched processes surrounded not only the primary glioma focus, but also all sites of tumor invasion in the nervous tissue. Expression of EBA (blood-brain barrier marker) was disturbed and synthesis of AMVB1 (endothelial antigen) increased in neoplastic endotheliocytes, which suggested pronounced functional restructuring of the blood-tumor barrier in comparison with the blood-brain barrier. The phenomenon of predominant expression of GFAP and AMVB1 in the tumor tissue can be used for the development of systems for targeted drug transport into the tumor by means of appropriate antibodies.
Journal of Neuro-Oncology, 1994
A glioma cell line, CNS-1, was developed in the inbred Lewis rat to obtain a histocompatible astrocytoma cell line with infiltrative and growth patterns that more closely simulate those observed in human gliomas. Rats were given weekly intravenous injections for a six month period with N-nitroso-N-methylurea to produce neoplasm in the central nervous system. Intracranial tumor was isolated, enzymatically and mechanically digested, and placed into culture. The tumor cell line injected subcutaneously on the flanks of Lewis rats grew extensively in situ as cohesive tumor masses but did not metastasize. Intracranially, CNS-1 demonstrated single cell infiltration of paranchyma and leptomeningeal, perivascular, and periventricular spread with expansion of the tumor within choroid plexus stroma. CNS-1 cells titrated in right frontal brain of Lewis rats at 105, 5 x 105, 105, 5 x 104 cells per group had mean survival times ranging from 20.5 to 30.2 days. CNS-1 was immunoreactive for glial fibrillary acidic protein, $100 protein, vimentin, neural cell adhesion molecule, retinoic acid receptor ~, intercellular adhesion molecule, and neuron specific enolase. The CNS-1 cells commonly had one or more trisomies of chromosomes 11,13 or 18; losses, possibly random, of chromosomes (3, 5,19, 30, X or Y) were noticed, and a marker chromosome made up of approximately 3 chromosomes was usual. Comparisons of CNS-1 to 9L gliosarcoma tumor were made. The glial CNS-1 tumor model provides an excellent system in which to investigate a variety of immunological therapeutic modalities. It spreads within brain in a less cohesive mass than 9L and is accepted without rejection in non-central nervous system sites by Lewis rats.
The American journal of pathology, 1987
Explants derived from human gliomas have been characterized with respect to their cellular outgrowth pattern after 1-22 weeks in culture. A mat of cells which were fibronectin (FN)-positive and glial fibrillary acidic protein (GFAP)-negative (hereafter designated FN+ cells) with a polygonal, flat morphology covered the growth substrate in a swirling pattern for a mean diameter of 9.2 mm around FN+ explants. FN+ cells showed ruffled plasmalemma, dilated rough endoplasmic reticulin (RDR), and extracellular filamentous strands. Rare desmosomes were compatible with at most minor leptomeningeal components or differentiation. FN+ cells predominated in six of seven cultures at passage 2, and their features were the same from various high-grade gliomas and gliosarcoma. Around other explants, elongated or stellate cells which were GFAP+ and FN- grew in a netlike pattern with little cell-to-cell contact. These GFAP+ cells surrounded explants at a mean diameter of 2 mm, substantially less than...
Experimental nodel of C6 brain tumors in athymic rats
Arquivos de Neuro-Psiquiatria, 2008
Malignant brain tumor experimental models tend to employ cells that are immunologically compatible with the receptor animal. In this study, we have proposed an experimental model of encephalic tumor development by injecting C6 cells into athymic Rowett rats, aiming at reaching a model which more closely resembles to the human glioma tumor. In our model, we observed micro-infiltration of tumor cell clusters in the vicinity of the main tumor mass, and of more distal isolated tumor cells immersed in normal encephalic parenchyma. This degree of infiltration is superior to that usually observed in other C6 models.
Characterization of an established human malignant glioma cell line: LN-18
Acta Neuropathologica, 1981
A human malignant glioma cell line, has been established in monolayer culture and subcultured for more than 115 passages. LN-18 cells grow in vitro as bipolar or stellate cells with pleomorphic nuclei, have a doubling time of about 72 h and a plating efficiency of 3 %. The glial nature of these cells has been assessed by ultrastructural examination. The synthesis of glial fibrillary acidic and S-100 proteins could not be demonstrated, although the initial biopsy tissue and the early cultures were positive for the former. The presence of [a-like antigens on the surface of these cells was demonstrated using allo and xeno antisera. LN-18 cells were also shown to synthesize large quantities of fibronectin. The injection of LN-18 cells into nude mice induced the formation of solid tumor masses that could be retransplanted every 3 weeks and showed a morphology comparable to that of the initial biopsy. Karyotype analysis revealed the presence of three marker chromosomes, constantly present before and after hetero-transplantation.