Neuron-associated class III ?-tubulin isotype, retinal S-antigen, synaptophysin, and glial fibrillary acidic protein in human medulloblastomas: a clinicopathological analysis of 36 cases

Maraziotis, Theodoros; Perentes, Elias; Karamitopoulou, Eva; Nakagawa, Yoshio; Gessaga, E.; Probst, A.; Frankfurter, Anthony

doi:10.1007/bf00227661

Cited by 61 publications

(24 citation statements)

References 29 publications

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“…In normal cerebellar development, class III [~-tubulin , MAP2, and tan (Yachnis et aI., 1993) are expressed in the external granular layer of Obersteiner, which is proposed to be one of the sites of origin of medulloblastomas (Kadin et al, 1970). Class III ]3-tubulin and synaptophysin have been previously demonstrated in surgical specimens of medulloblastomas in a differentiation-dependent manner (Katsetos et aI., 1989;Maraziotis et al, 1992). The present study, however, is the first to detail the presence of class III ]3-tubulin or tau protein in the D283 Med line.…”

Section: Discussionmentioning

confidence: 99%

“…and in a variety of other normal and neoplastic cells (Haimoto et al, I985;Vinores et al, I984, 1986;Vinores & Rubinstein, 1985). Retinal S-antigen has been reported in medulloblastomas (Bonnin & Perentes, 1988;Koff et al, 1987;Maraziotis et aI., 1992;Perentes, 1991) and its presence has suggested differentiation along photoreceptor lines or a link to pineoblastoma (Maraziotis et al, 1992;Russell & Rubinstein, 1989), but none of the medulloblastomas in the present study showed any positivity for the antigen.…”

Section: Discussionmentioning

confidence: 99%

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Neuron-associated class III ?-tubulin, tau, and MAP2 in the D-283 Med cell line and in primary explants of human medulloblastoma

Vinores

Herman²,

Katsetos³

et al. 1994

Histochem J

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The D283 Med human medulloblastoma cell line and primary explants of five surgically excised medulloblastomas were cultured using a three-dimensional Gelfoam matrix system. The cultures were evaluated immunohistochemically for a series of antigenic determinants associated with neuronal or glial differentiation. Focal immunolocalization of class III beta-tubulin, microtubule-associated protein 2 (MAP2), and to a lesser degree tau, was demonstrated in all cultures. Class III beta-tubulin isotype, MAP2, and tau protein were also detected by immunoblot in Gelfoam matrix cultures, monolayer cultures, and suspension cultures of D283 Med cells. Staining for neurofilament protein epitopes was highly variable, even among different cultures derived from the same original tumour, but time-dependent changes in neurofilament protein, which may have reflected neuronal differentiation, were not consistently shown. Widespread gamma-enolase and focal synaptophysin reactivities were visualized in all cultures, but no S-antigen staining was detected. Leu 7 labelling was variably present in half of the cultures of D283 Med cells, but was more abundant in explants derived from four of the five original tumours. Vimentin was consistently found in D283 Med cultures at all time points. No immunoreactivity for glial fibrillary acidic protein was detected in the D283 Med cell line. Conversely, staining for this protein was demonstrated in scattered astrocytic cells in the surgical specimens of all five medulloblastomas. Concomitant with increased time in culture, three of the primary tumours displayed increased numbers of glial fibrillary acidic protein-positive cells when cultured in the Gelfoam system, but the other two tumours had a minimal astrocytic component.(ABSTRACT TRUNCATED AT 250 WORDS)

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Neuron-associated class III ?-tubulin, tau, and MAP2 in the D-283 Med cell line and in primary explants of human medulloblastoma

Vinores

Herman²,

Katsetos³

et al. 1994

Histochem J

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“…In the context of growth and differentiation of cerebellar medulloblastomas, the ␤III-tubulin isotype is expressed in a differentiation-dependent manner and is associated with neoplastic neuritogenesis [Katsetos et al, , 1995Maraziotis et al, 1992] (Fig. 1e).…”

Section: Class III ␤-Tubulin In Cerebellar Medulloblastomasmentioning

confidence: 99%

Class III β‐tubulin in human development and cancer

Katsetos

Herman²,

Mörk

2003

Cell Motil. Cytoskeleton

262

188

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The differential cellular expression of class III ␤-tubulin isotype (␤III) is reviewed in the context of human embryological development and neoplasia. As compared to somatic organs and tissues, ␤III is abundant in the central and peripheral nervous systems (CNS and PNS) where it is prominently expressed during fetal and postnatal development. As exemplified in cerebellar and sympathoadrenal neurogenesis, the distribution of ␤III is neuron-associated, exhibiting distinct temporospatial gradients according to the regional neuroepithelia of origin. However, transient expression of this protein is also present in the subventricular zones of the CNS comprising putative neuronal-and/or glial precursor cells, as well as in Kulchitsky neuroendocrine cells of the fetal respiratory epithelium. This temporally restricted, potentially non-neuronal expression may have implications in the identification of presumptive neurons derived from embryonic stem cells. In adult tissues, the distribution of ␤III is almost exclusively neuron-specific. Altered patterns of expression are noted in cancer. In "embryonal"-and "adult-type" neuronal tumors of the CNS and PNS, ␤III is associated with neuronal differen- Abbreviations: bHLH, basic helix-loop-helix; ␤III, class III ␤-tubulin isotype, CNE , central nervous system enhancer; CNS, central nervous system; EGL, external granule layer; MAP, microtubule-associated protein; NCAM, neural cell adhesion molecule; OPC, oligodendrocyte precursor cell; PCNA, proliferating cell nuclear antigen; PNS, peripheral nervous system; pRb, retinoblastoma tumor suppressor protein; PSA, polysialated; SVZ, subventricular zone; WHO, World Health Organization. tiation and decreased cell proliferation. In contrast, the presence of ␤III in gliomas and lung cancer is associated with an ascending histological grade of malignancy. Thus, ␤III expression in neuronal tumors is differentiation-dependent, while in non-neuronal tumors it is aberrant and/or represents "dedifferentiation" associated with the acquisition of progenitor-like phenotypic properties. Increased expression in various epithelial cancer cell lines is associated with chemoresistance to taxanes. Because ␤III is present in subpopulations of neoplastic, but not in normal differentiated glial or somatic epithelial cells, the elucidation of mechanisms responsible for the altered expression of this isotype may provide insights into the role of the microtubule cytoskeleton in tumorigenesis and tumor progression. Cell Motil. Cytoskeleton 55: 77-96, 2003.

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“…It is also well accepted, however, that GFAP may be found much less commonly in CNS tumor cells that, although neuroepithelial in origin, are not strictly speaking astrocytic, including the oligodendroglioma, ependymoma, primitive neuroectodermal tumor, and choroid plexus papilloma. [19,56,65,73,77,92,95] In these tumor types, care must be taken to distinguish between GFAP-positive neoplastic cells and entrapped or peritumoral reactive astrocytes, both of which express abundant GFAP. [19,77] Interestingly, GFAP may be expressed in cells outside the CNS, such as nonmyelinating Schwann cells, the epithelium of the lens, the epithelial cells of salivary glands and their neoplasms, and neoplastic cells of mullerian origin.…”

Section: Glial Fibrillary Acidic Protein: a Marker For Cells And Tumomentioning

confidence: 99%

Role of glial filaments in cells and tumors of glial origin: a review

Rutka¹,

Murakami²,

Dirks³

et al. 1997

FOC

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In the adult human brain, normal astrocytes constitute nearly 40% of the total central nervous system (CNS) cell population and may assume a star-shaped configuration resembling epithelial cells insofar as the astrocytes remain intimately associated, through their cytoplasmic extensions, with the basement membrane of the capillary endothelial cells and the basal lamina of the glial limitans externa. Although their exact function remains unknown, in the past, astrocytes were thought to subserve an important supportive role for neurons, providing a favorable ionic environment, modulating extracellular levels of neurotransmitters, and serving as spacers that organize neurons. In immunohistochemical preparations, normal, reactive, and neoplastic astrocytes may be positively identified and distinguished from other CNS cell types by the expression of the astrocyte-specific intermediate filament glial fibrillary acidic protein (GFAP). This GFAP is a 50-kD intracytoplasmic filamentous protein that constitutes a portion of, and is specific for, the cytoskeleton of the astrocyte. This protein has proved to be the most specific marker for cells of astrocytic origin under normal and pathological conditions. Interestingly, with increasing astrocytic malignancy, there is progressive loss of GFAP production. As the human gene for GFAP has now been cloned and sequenced, this review begins with a summary of the molecular biology of GFAP including the proven utility of the GFAP promoter in targeting genes of interest to the CNS in transgenic animals. Based on the data provided the authors argue cogently for an expanded role of GFAP in complex cellular events such as cytoskeletal reorganization, maintenance of myelination, cell adhesion, and signaling pathways. As such, GFAP may not represent a mere mechanical integrator of cellular space, as has been previously thought. Rather, GFAP may provide docking sites for important kinases that recognize key cellular substrates that enable GFAP to form a dynamic continuum with microfilaments, integrin receptors, and the extracellular matrix.

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Neuron-associated class III ?-tubulin isotype, retinal S-antigen, synaptophysin, and glial fibrillary acidic protein in human medulloblastomas: a clinicopathological analysis of 36 cases

Cited by 61 publications

References 29 publications

Neuron-associated class III ?-tubulin, tau, and MAP2 in the D-283 Med cell line and in primary explants of human medulloblastoma

Neuron-associated class III ?-tubulin, tau, and MAP2 in the D-283 Med cell line and in primary explants of human medulloblastoma

Class III β‐tubulin in human development and cancer

Role of glial filaments in cells and tumors of glial origin: a review

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