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Primary ciliogenesis defects are associated with human astrocytoma/glioblastoma cells
BACKGROUND: Primary cilia are non-motile sensory cytoplasmic organelles that have been implicated in signal transduction, cell to cell communication, left and right pattern embryonic development, sensation of fluid flow, regulation of calcium levels, mechanosensation, growth factor signaling and cel...
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Formato: | Texto |
Lenguaje: | English |
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BioMed Central
2009
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2806408/ https://www.ncbi.nlm.nih.gov/pubmed/20017937 http://dx.doi.org/10.1186/1471-2407-9-448 |
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author | Moser, Joanna J Fritzler, Marvin J Rattner, Jerome B |
author_facet | Moser, Joanna J Fritzler, Marvin J Rattner, Jerome B |
author_sort | Moser, Joanna J |
collection | PubMed |
description | BACKGROUND: Primary cilia are non-motile sensory cytoplasmic organelles that have been implicated in signal transduction, cell to cell communication, left and right pattern embryonic development, sensation of fluid flow, regulation of calcium levels, mechanosensation, growth factor signaling and cell cycle progression. Defects in the formation and/or function of these structures underlie a variety of human diseases such as Alström, Bardet-Biedl, Joubert, Meckel-Gruber and oral-facial-digital type 1 syndromes. The expression and function of primary cilia in cancer cells has now become a focus of attention but has not been studied in astrocytomas/glioblastomas. To begin to address this issue, we compared the structure and expression of primary cilia in a normal human astrocyte cell line with five human astrocytoma/glioblastoma cell lines. METHODS: Cultured normal human astrocytes and five human astrocytoma/glioblastoma cell lines were examined for primary cilia expression and structure using indirect immunofluorescence and electron microscopy. Monospecific antibodies were used to detect primary cilia and map the relationship between the primary cilia region and sites of endocytosis. RESULTS: We show that expression of primary cilia in normal astrocytes is cell cycle related and the primary cilium extends through the cell within a unique structure which we show to be a site of endocytosis. Importantly, we document that in each of the five astrocytoma/glioblastoma cell lines fully formed primary cilia are either expressed at a very low level, are completely absent or have aberrant forms, due to incomplete ciliogenesis. CONCLUSIONS: The recent discovery of the importance of primary cilia in a variety of cell functions raises the possibility that this structure may have a role in a variety of cancers. Our finding that the formation of the primary cilium is disrupted in cells derived from astrocytoma/glioblastoma tumors provides the first evidence that altered primary cilium expression and function may be part of some malignant phenotypes. Further, we provide the first evidence that ciliogenesis is not an all or none process; rather defects can arrest this process at various points, particularly at the stage subsequent to basal body association with the plasma membrane. |
format | Text |
id | pubmed-2806408 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-28064082010-01-14 Primary ciliogenesis defects are associated with human astrocytoma/glioblastoma cells Moser, Joanna J Fritzler, Marvin J Rattner, Jerome B BMC Cancer Research Article BACKGROUND: Primary cilia are non-motile sensory cytoplasmic organelles that have been implicated in signal transduction, cell to cell communication, left and right pattern embryonic development, sensation of fluid flow, regulation of calcium levels, mechanosensation, growth factor signaling and cell cycle progression. Defects in the formation and/or function of these structures underlie a variety of human diseases such as Alström, Bardet-Biedl, Joubert, Meckel-Gruber and oral-facial-digital type 1 syndromes. The expression and function of primary cilia in cancer cells has now become a focus of attention but has not been studied in astrocytomas/glioblastomas. To begin to address this issue, we compared the structure and expression of primary cilia in a normal human astrocyte cell line with five human astrocytoma/glioblastoma cell lines. METHODS: Cultured normal human astrocytes and five human astrocytoma/glioblastoma cell lines were examined for primary cilia expression and structure using indirect immunofluorescence and electron microscopy. Monospecific antibodies were used to detect primary cilia and map the relationship between the primary cilia region and sites of endocytosis. RESULTS: We show that expression of primary cilia in normal astrocytes is cell cycle related and the primary cilium extends through the cell within a unique structure which we show to be a site of endocytosis. Importantly, we document that in each of the five astrocytoma/glioblastoma cell lines fully formed primary cilia are either expressed at a very low level, are completely absent or have aberrant forms, due to incomplete ciliogenesis. CONCLUSIONS: The recent discovery of the importance of primary cilia in a variety of cell functions raises the possibility that this structure may have a role in a variety of cancers. Our finding that the formation of the primary cilium is disrupted in cells derived from astrocytoma/glioblastoma tumors provides the first evidence that altered primary cilium expression and function may be part of some malignant phenotypes. Further, we provide the first evidence that ciliogenesis is not an all or none process; rather defects can arrest this process at various points, particularly at the stage subsequent to basal body association with the plasma membrane. BioMed Central 2009-12-17 /pmc/articles/PMC2806408/ /pubmed/20017937 http://dx.doi.org/10.1186/1471-2407-9-448 Text en Copyright ©2009 Moser et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Moser, Joanna J Fritzler, Marvin J Rattner, Jerome B Primary ciliogenesis defects are associated with human astrocytoma/glioblastoma cells |
title | Primary ciliogenesis defects are associated with human astrocytoma/glioblastoma cells |
title_full | Primary ciliogenesis defects are associated with human astrocytoma/glioblastoma cells |
title_fullStr | Primary ciliogenesis defects are associated with human astrocytoma/glioblastoma cells |
title_full_unstemmed | Primary ciliogenesis defects are associated with human astrocytoma/glioblastoma cells |
title_short | Primary ciliogenesis defects are associated with human astrocytoma/glioblastoma cells |
title_sort | primary ciliogenesis defects are associated with human astrocytoma/glioblastoma cells |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2806408/ https://www.ncbi.nlm.nih.gov/pubmed/20017937 http://dx.doi.org/10.1186/1471-2407-9-448 |
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