Loss of GFAP expression in high-grade astrocytomas does not contribute to tumor development or progression (original) (raw)
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Anaplasia and heterogeneity of GFAP expression in gliomas.Tumori 72, 163-170
Tumori
GFAP (glial fibrillary acidic protein) distribution was investigated in selected areas of glioblastomas and astrocytomas. The proliferating cell population of glioblastomas was GFAP negative and contained many mitoses which were also negative. The old, deeply located areas were composed of cells with visible cytoplasm, intensely GFAP-positive; mitoses in these areas were both GFAP-positive and negative. GFAP-positive reactive astrocytes, once trapped in the tumor, were no longer distinguishable from positive tumor cells. They sometimes contained mitoses. In astrocytoma, anaplasia was due to the development of a GFAP-negative population with negative mitoses. The problem of dedifferentiation and differentiation of malignant gliomas in discussed taking into account the possibility that malignancy may be due to increasing mutation rates of tumors. The problem of redifferentiation of already dedifferentiated cells is also discussed.
Anaplasia and heterogeneity of GFAP expression in gliomas
Tumori, 1986
GFAP (glial fibrillary acidic protein) distribution was investigated in selected areas of glioblastomas and astrocytomas. The proliferating cell population of glioblastomas was GFAP negative and contained many mitoses which were also negative. The old, deeply located areas were composed of cells with visible cytoplasm, intensely GFAP-positive; mitoses in these areas were both GFAP-positive and negative. GFAP-positive reactive astrocytes, once trapped in the tumor, were no longer distinguishable from positive tumor cells. They sometimes contained mitoses. In astrocytoma, anaplasia was due to the development of a GFAP-negative population with negative mitoses. The problem of dedifferentiation and differentiation of malignant gliomas in discussed taking into account the possibility that malignancy may be due to increasing mutation rates of tumors. The problem of redifferentiation of already dedifferentiated cells is also discussed.
Inducible expression of glial fibrillary acidic protein in HT-1080 human fibrosarcoma cells
Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research, 1996
Glial fibrillary acidic protein (GFAP) is an intermediate filament protein expressed almost exclusively by glial cells of the central nervous system. We have previously transfected GFAP-negative human astrocytoma cells with the gene for GFAP and have demonstrated that GFAP transfection decreases astrocytoma proliferation and alters astrocytoma morphology. To determine if the same cellular responses could be elicited upon GFAP transfection of nonglial tumor cells, in the present study we have transfected a GFAP-negative human malignant fibrosarcoma cell line (HT-1080) with a cDNA containing the entire coding sequence of the human GFAP gene under the control of an inducible metallothionein promoter. Stably transfected HT-1080 clones were identified that are GFAP-positive by PCR and immunocytochemistry. GFAP-positive HT-1080 fibrosarcoma cells also demonstrate a decrease in tumor cell proliferation, altered morphological features characterized by cell elongation and cytoplasmic process...
Journal of Neurosurgery, 1985
✓ Tissues from 12 metastatic tumors of the brain were studied immunohistochemically with an antiserum to a glia-specific protein, astroprotein (glial fibrillary acidic protein, GFAP). Emphasis was laid on demonstrating the tissue architecture of metastatic lesions incorporating brain-derived components (astrocytes and glial fibers). Of 12 samples, 11 manifested a number of irregular indentations at the tumor surface. These indentations, which contained astrocytic elements, extended into the tumor tissue in a tapering fashion. In seven cases, the deeper stromal portions of the tumor also contained astroprotein (GFAP)-positive elements. The presence of this glia-specific protein suggests that the stroma of the tumor tissue may in part be derived from preexisting brain tissue. This peculiar tissue architecture of the tumor supports the hypothesis that some of the blood vessels that are located in the stroma of the tumor tissue are also derived from the brain. These observations may be ...
Correlation of B-FABP and GFAP expression in malignant glioma
Oncogene, 1998
The murine brain fatty acid binding protein (B-FABP) is encoded by a developmentally regulated gene that is expressed in radial glial cells and immature astrocytes. We have cloned the human B-FABP gene and have mapped it to chromosome 6q22-23. We show that B-FABP mRNA is expressed in human malignant glioma tumor biopsies and in a subset of malignant glioma cell lines, as well as in human fetal retina and brain. Malignant glioma tumors are characterized by cytoplasmic bundles of glial fibrillary acidic protein (GFAP), a protein normally expressed in mature astrocytes. Establishment of malignant glioma cell lines often results in loss of GFAP. The subset of malignant glioma cell lines that express GFAP mRNA also express B-FABP mRNA. Co-localization experiments in cell lines indicate that the same cells produce both GFAP and B-FABP. We suggest that some malignant gliomas may be derived from astrocytic precursor cells which can express proteins that are normally produced at different developmental stages in the astrocytic differentiation pathway.
Jordan Medical Journal, 2011
Objectives: The aims of this study are to identify the Immunohistochemical (IHC) expression of Glial Fibrillary Acidic Protein (GFAP) in different types of neuroepithelial tumors in Mosul city and to correlate the results with grade of tumor, with the results of other studies and to assess the diagnostic role of GFAP in the diagnonsis of neuroepithelial tumors and their differentiation from neuroglial tumors. Patients and Methods: This study included 56 cases of neuroepithelial tumors. 22 cases were collected during the period extending from October 2007 to May 2008. (The rest of the cases were retrieved from a filing system extending back to 2004). In addition to two miscellaneous tumors, (one meningioma and the other secondary adenocarcinoma). All cases were obtained from Al-Jamhuri Teaching Hospital in the western side of Mosul City, Northern Iraq and some private laboratories. Typing and grading of the tumors were done according to World Health Organization (WHO) classification system. IHC procedure was done for GFAP using polyclonal antibodies and chromogen visualizing system. A semi-quantitative histochemical score was used to record the results of GFAP staining according to the system established by Catherine L. Nutt et al. Results: Thirty seven cases were diagnosed as astrocytoma, while 8 cases out of ependymoma, 4 cases of oligodendroglioma, and three cases medulloblastoma were shown. In addition, this study revealed that one case for each of: oligoastrocytoma, Medulloepithelioma, atypical rhabdoid tumor and astroblastoma. Glial Fibrillary Acidic Protein (GFAP) was expressed in 85.7% of neuroepithelial tumors. Higher GFAP positivity was found in glioma than other types of neuroepithelial tumors (P value <0.05). On the other hand, GFAP was expressed in (36%) of astrocytoma. In oligodendroglioma, 3 cases out of 4 were positive while all cases of ependymoma were positive. In addition, oligoastrocytoma was positive while the remaining cases of neuroepithelial tumors were negative. In general, each type of glioma had special staining pattern of GFAP. GFAP status was found to be inversely related with the grade of glioma (P value <0.05). Conclusions: GFAP is expressed more frequently in glioma than in other neuroepithelial tumors and this result is similar to many other studies done outside Iraq and it is correlated inversely with the grade of tumor. So, it is a valid supplementary diagnostic procedure for neuroepithelial tumors and a reliable marker to differentiate between glial from non-glial tumors on one hand and between different types of glial tumors on the other hand.
The Journal of Cell Biology, 1994
Astroglial cells play an important role in orchestrating the migration and positioning of neurons during central nervous system development. Primary astroglia, as well as astrocytoma cells will extend long stable processes when co-cultured with granule neurons. In order to determine the function of the glial fibrillary acidic protein (GFAP), the major intermediate filament protein in astroglia and astrocytoma cells, we suppressed the expression of GFAP by stable transfection of an anti-sense GFAP construct in human astrocytoma U251MG cells. The resulting AS2-U251 cells can no longer extend stable processes in the presence of granule neurons. To show that this effect is due specifically to the absence of GFAP, we reintroduced a fully encoding rat brain GFAP cDNA into these AS2-U251 cells. The resulting rat GFAP appeared as a filamentous network and the reexpression of GFAP rescued the ability of these astrocytoma cells to form stable processes when co-cultured with neurons. From thes...
Roles of the functional loss of p53 and other genes in astrocytoma tumorigenesis and progression
Neuro- …, 1999
Loss of function in the p53 tumor suppressor gene due to mutation occurs early in astrocytoma tumorigenesis in about 30-40% of cases. This is believed to confer a growth advantage to the cells, allowing them to clonally expand due to loss of the p53-controlled G 1 checkpoint and apoptosis. Genetic instability due to the impaired ability of p53 to mediate DNA damage repair further facilitates the acquisition of new genetic abnormalities, leading to malignant progression of an astrocytoma into anaplastic astrocytoma. This is re ected by a high rate of p53 mutation (60-70%) in anaplastic astrocytomas. The cell cycle control gets further compromised in astrocytoma by alterations in one of the G 1 /S transition control genes, either loss of the p16/CDKN2 or RB genes or ampli cation of the cyclin D gene. The nal progression process leading to glioblastoma multiforme seems to need additional genetic abnormalities in the long arm of chromosome 10; one of which is deletion and/or functional loss of the PTEN/MMAC1 gene. Glioblastomas also occur as primary (de novo) lesions in patients of older age, without p53 gene loss but with ampli cation of the epidermal growth factor receptor (EGFR) gene. In contrast to the secondary glioblastomas that evolve from astrocytoma cells with p53 mutations in younger patients, primary glioblastomas seem to be resistant to radiation therapy and thus show a poorer prognosis. The evaluation and design of therapeutic modalities aimed at preventing malignant progression of astrocytomas and glioblastomas should now be based on stratifying patients with astrocytic tumors according to their genetic diagnosis. Neuro-Oncology 1, 124-137, 1999 (Posted to Neuro-Oncology [serial online], Doc. 98-17, April 30, 1999
Pathological and Molecular Progression of Astrocytomas in a GFAP:12V-Ha-Ras Mouse Astrocytoma Model
The American Journal of Pathology, 2005
We previously characterized a genetically engineered mouse astrocytoma model with embryonic astrocytespecific, activated 12 V-Ha-RAS (GFAP-RAS) transgenesis. The GFAP-RAS line Ras-B8 appears normal at birth, but 50% of mice die by 4 months from low-and high-grade astrocytomas. We examined the development and progression of astrocytomas in the Ras-B8 genetically engineered mouse. At embryonic day 16.5 (E16.5), there were no pathological differences compared to control littermates, aside from transgene expression. Diffuse astroglial hyperplasia was the first distinguishing feature in the 1-week-old Ras-B8 mice; however, these astrocytes were not transformed in vitro or in vivo. From 3 to 8 weeks the incidence of low-grade astrocytomas progressively increased with 85% of 12-week-old mice harboring lowor high-grade astrocytomas, the latter characterized by increased proliferation, nuclear atypia, and angiogenesis. Tp53 mutations were detected in both astrocytoma grades, with high-grade astrocytomas expressing elevated levels of epidermal growth factor receptor and vascular endothelial growth factor, plus decreased levels of PTEN and p16, similar to human astrocytomas. We postulate that expression of 12 V-Ha-RAS in astroglial precursors induces astroglial hyperplasia, but transformation and subsequent progression requires additional molecular alterations resulting from aberrant activated p21-RAS. Of interest, many of these acquired alterations occur in human astrocytomas, further validating GFAP-RAS as a useful model for studying astrocytoma development and progression.