Aberrant nestin expression during ethylnitrosourea-(ENU)-induced neurocarcinogenesis
Nestin is a unique intermediate filament protein. While it is robustly expressed in developing brain, postnatal expression is limited to the brain's subventricular zone (SVZ) and endothelial cells. Reexpression occurs, however, under several pathological conditions, including injury and neoplas...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2004-04-01
|
| Series: | Neurobiology of Disease |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996103002511 |
| _version_ | 1818616210840879104 |
|---|---|
| author | Taichang Jang N.Scott Litofsky Thomas W Smith Alonzo H Ross Lawrence D Recht |
| author_facet | Taichang Jang N.Scott Litofsky Thomas W Smith Alonzo H Ross Lawrence D Recht |
| author_sort | Taichang Jang |
| collection | DOAJ |
| description | Nestin is a unique intermediate filament protein. While it is robustly expressed in developing brain, postnatal expression is limited to the brain's subventricular zone (SVZ) and endothelial cells. Reexpression occurs, however, under several pathological conditions, including injury and neoplasia. We hypothesized that nestin would be a sensitive marker of early neoplasia after transplacental exposure of rats to ethylnitrosourea (ENU). Rats of various ages were administered bromodeoxyuridine (BudR) before sacrifice, and brain sections were examined for proliferative cells and several immunohistochemical markers, including nestin. Additional rats were examined after a stab wound injury to assess the expression of two of these markers, GFAP and nestin, in reactive astrocytes. All ENU-induced brain tumors (n = 9) were classified as gliomas (astrocytomas or oligoastrocytomas) based on their histology and immunophenotype. Nestin expression was noted in all tumors examined and was present in tumor cells as well as endothelial cells. During tumor development, we consistently noted nestin-expressing cells bearing multiple processes distributed throughout brain parenchyma. Both single cells and multiple cell clusters were observed as early as postnatal day 30 in all ENU-exposed brains examined (n = 11). Such distinctive nestin-expressing cells were not seen in nestin-stained control brains or ENU-exposed brains stained for GFAP or vimentin, nor was such a cell seen in a stab wound model used to assess reactive astrocytosis. While the number of these clusters was highly variable among rats, their size increased between 30 and 90 days. The data suggest that these nestin-expressing cells represent an early stage of the neoplastic process. It remains to be determined whether these cells become apparent at 30 days of age due to “dedifferentiation” of a local resident astrocyte or astrocyte precursor cell or migration of a relatively undifferentiated precursor/stem cell from the SVZ. |
| first_indexed | 2024-12-16T16:46:11Z |
| format | Article |
| id | doaj.art-a6b3b103484f4405aae1958151fbb2ee |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-12-16T16:46:11Z |
| publishDate | 2004-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-a6b3b103484f4405aae1958151fbb2ee2022-12-21T22:24:11ZengElsevierNeurobiology of Disease1095-953X2004-04-01153544552Aberrant nestin expression during ethylnitrosourea-(ENU)-induced neurocarcinogenesisTaichang Jang0N.Scott Litofsky1Thomas W Smith2Alonzo H Ross3Lawrence D Recht4Department of Surgery (Neurosurgery), University of Massachusetts Medical School, Worcester, MA 01655, USA; Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655, USA; Department of Neurology, University of Massachusetts Medical School, Worcester, MA 01655, USA; Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01655 USADepartment of Surgery (Neurosurgery), University of Massachusetts Medical School, Worcester, MA 01655, USA; Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655, USA; Department of Neurology, University of Massachusetts Medical School, Worcester, MA 01655, USA; Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01655 USADepartment of Surgery (Neurosurgery), University of Massachusetts Medical School, Worcester, MA 01655, USA; Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655, USA; Department of Neurology, University of Massachusetts Medical School, Worcester, MA 01655, USA; Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01655 USADepartment of Surgery (Neurosurgery), University of Massachusetts Medical School, Worcester, MA 01655, USA; Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655, USA; Department of Neurology, University of Massachusetts Medical School, Worcester, MA 01655, USA; Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01655 USADepartment of Surgery (Neurosurgery), University of Massachusetts Medical School, Worcester, MA 01655, USA; Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655, USA; Department of Neurology, University of Massachusetts Medical School, Worcester, MA 01655, USA; Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01655 USANestin is a unique intermediate filament protein. While it is robustly expressed in developing brain, postnatal expression is limited to the brain's subventricular zone (SVZ) and endothelial cells. Reexpression occurs, however, under several pathological conditions, including injury and neoplasia. We hypothesized that nestin would be a sensitive marker of early neoplasia after transplacental exposure of rats to ethylnitrosourea (ENU). Rats of various ages were administered bromodeoxyuridine (BudR) before sacrifice, and brain sections were examined for proliferative cells and several immunohistochemical markers, including nestin. Additional rats were examined after a stab wound injury to assess the expression of two of these markers, GFAP and nestin, in reactive astrocytes. All ENU-induced brain tumors (n = 9) were classified as gliomas (astrocytomas or oligoastrocytomas) based on their histology and immunophenotype. Nestin expression was noted in all tumors examined and was present in tumor cells as well as endothelial cells. During tumor development, we consistently noted nestin-expressing cells bearing multiple processes distributed throughout brain parenchyma. Both single cells and multiple cell clusters were observed as early as postnatal day 30 in all ENU-exposed brains examined (n = 11). Such distinctive nestin-expressing cells were not seen in nestin-stained control brains or ENU-exposed brains stained for GFAP or vimentin, nor was such a cell seen in a stab wound model used to assess reactive astrocytosis. While the number of these clusters was highly variable among rats, their size increased between 30 and 90 days. The data suggest that these nestin-expressing cells represent an early stage of the neoplastic process. It remains to be determined whether these cells become apparent at 30 days of age due to “dedifferentiation” of a local resident astrocyte or astrocyte precursor cell or migration of a relatively undifferentiated precursor/stem cell from the SVZ.http://www.sciencedirect.com/science/article/pii/S0969996103002511Ethylnitrosourea (ENU)GFAPGlial neoplasmsNestinNeurocarcinogenesisRat |
| spellingShingle | Taichang Jang N.Scott Litofsky Thomas W Smith Alonzo H Ross Lawrence D Recht Aberrant nestin expression during ethylnitrosourea-(ENU)-induced neurocarcinogenesis Neurobiology of Disease Ethylnitrosourea (ENU) GFAP Glial neoplasms Nestin Neurocarcinogenesis Rat |
| title | Aberrant nestin expression during ethylnitrosourea-(ENU)-induced neurocarcinogenesis |
| title_full | Aberrant nestin expression during ethylnitrosourea-(ENU)-induced neurocarcinogenesis |
| title_fullStr | Aberrant nestin expression during ethylnitrosourea-(ENU)-induced neurocarcinogenesis |
| title_full_unstemmed | Aberrant nestin expression during ethylnitrosourea-(ENU)-induced neurocarcinogenesis |
| title_short | Aberrant nestin expression during ethylnitrosourea-(ENU)-induced neurocarcinogenesis |
| title_sort | aberrant nestin expression during ethylnitrosourea enu induced neurocarcinogenesis |
| topic | Ethylnitrosourea (ENU) GFAP Glial neoplasms Nestin Neurocarcinogenesis Rat |
| url | http://www.sciencedirect.com/science/article/pii/S0969996103002511 |
| work_keys_str_mv | AT taichangjang aberrantnestinexpressionduringethylnitrosoureaenuinducedneurocarcinogenesis AT nscottlitofsky aberrantnestinexpressionduringethylnitrosoureaenuinducedneurocarcinogenesis AT thomaswsmith aberrantnestinexpressionduringethylnitrosoureaenuinducedneurocarcinogenesis AT alonzohross aberrantnestinexpressionduringethylnitrosoureaenuinducedneurocarcinogenesis AT lawrencedrecht aberrantnestinexpressionduringethylnitrosoureaenuinducedneurocarcinogenesis |