Endothelial-like malignant glioma cells in dynamic three dimensional culture identifies a role for VEGF and FGFR in a tumor-derived angiogenic response
Aims: Recent studies have observed that cells from high-grade glial tumors are capable of assuming an endothelial phenotype and genotype, a process termed ‘vasculogenic mimicry’ (VM). Here we model and manipulate VM in dynamic 3-dimensional (3D) glioma cultures. Methods: The Rotary Cell Culture Syst...
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| Format: | Article |
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Impact Journals
2015
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| Online Access: | https://eprints.nottingham.ac.uk/31768/ |
| _version_ | 1848794269769269248 |
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| author | Smith, Stuart J. Ward, Jennifer H. Tan, Christopher Grundy, Richard G. Rahman, Ruman |
| author_facet | Smith, Stuart J. Ward, Jennifer H. Tan, Christopher Grundy, Richard G. Rahman, Ruman |
| author_sort | Smith, Stuart J. |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | Aims: Recent studies have observed that cells from high-grade glial tumors are capable of assuming an endothelial phenotype and genotype, a process termed ‘vasculogenic mimicry’ (VM). Here we model and manipulate VM in dynamic 3-dimensional (3D) glioma cultures. Methods: The Rotary Cell Culture System (RCCS) was used to derive large macroscopic glioma aggregates, which were sectioned for immunohistochemistry and RNA extracted prior to angiogenic array-PCR. Results: A 3D cell culture induced microenvironment (containing only glial cells) is sufficient to promote expression of the endothelial markers CD105, CD31 and vWF in a proportion of glioma aggregates in vitro. Many pro-angiogenic genes were upregulated in glioma aggregates and in primary explants and glioma cells were capable of forming tubular-like 3D structures under endothelial-promoting conditions. Competitive inhibition of either vascular endothelial growth factor or fibroblast growth factor receptor was sufficient to impair VM and downregulate the tumor-derived angiogenic response, whilst impairing tumor cell derived tubule formation. Glioma xenografts using the same cells reveal tumor-derived vessel-like structures near necrotic areas, consistent with widespread tumor-derived endothelial expression in primary glioma tissue. Conclusions: Our findings support studies indicating that tumor-derived endothelial cells arise in gliomas and describe a dynamic 3D culture as a bona fide model to interrogate the molecular basis of this phenomenon in vitro. Resistance to current anti-angiogenic therapies and the contribution of tumor derived endothelial cells to such resistance are amenable to study using the RCCS. |
| first_indexed | 2025-11-14T19:13:31Z |
| format | Article |
| id | nottingham-31768 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T19:13:31Z |
| publishDate | 2015 |
| publisher | Impact Journals |
| recordtype | eprints |
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| spelling | nottingham-317682020-05-04T17:11:40Z https://eprints.nottingham.ac.uk/31768/ Endothelial-like malignant glioma cells in dynamic three dimensional culture identifies a role for VEGF and FGFR in a tumor-derived angiogenic response Smith, Stuart J. Ward, Jennifer H. Tan, Christopher Grundy, Richard G. Rahman, Ruman Aims: Recent studies have observed that cells from high-grade glial tumors are capable of assuming an endothelial phenotype and genotype, a process termed ‘vasculogenic mimicry’ (VM). Here we model and manipulate VM in dynamic 3-dimensional (3D) glioma cultures. Methods: The Rotary Cell Culture System (RCCS) was used to derive large macroscopic glioma aggregates, which were sectioned for immunohistochemistry and RNA extracted prior to angiogenic array-PCR. Results: A 3D cell culture induced microenvironment (containing only glial cells) is sufficient to promote expression of the endothelial markers CD105, CD31 and vWF in a proportion of glioma aggregates in vitro. Many pro-angiogenic genes were upregulated in glioma aggregates and in primary explants and glioma cells were capable of forming tubular-like 3D structures under endothelial-promoting conditions. Competitive inhibition of either vascular endothelial growth factor or fibroblast growth factor receptor was sufficient to impair VM and downregulate the tumor-derived angiogenic response, whilst impairing tumor cell derived tubule formation. Glioma xenografts using the same cells reveal tumor-derived vessel-like structures near necrotic areas, consistent with widespread tumor-derived endothelial expression in primary glioma tissue. Conclusions: Our findings support studies indicating that tumor-derived endothelial cells arise in gliomas and describe a dynamic 3D culture as a bona fide model to interrogate the molecular basis of this phenomenon in vitro. Resistance to current anti-angiogenic therapies and the contribution of tumor derived endothelial cells to such resistance are amenable to study using the RCCS. Impact Journals 2015-06-02 Article PeerReviewed Smith, Stuart J., Ward, Jennifer H., Tan, Christopher, Grundy, Richard G. and Rahman, Ruman (2015) Endothelial-like malignant glioma cells in dynamic three dimensional culture identifies a role for VEGF and FGFR in a tumor-derived angiogenic response. Oncotarget, 6 (26). pp. 22191-22205. ISSN 1949-2553 vasculogenic mimicry rotary cell culture system angiogenesis glioma tumor-derived endothelium http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path[]=4339 doi:10.18632/oncotarget.4339 doi:10.18632/oncotarget.4339 |
| spellingShingle | vasculogenic mimicry rotary cell culture system angiogenesis glioma tumor-derived endothelium Smith, Stuart J. Ward, Jennifer H. Tan, Christopher Grundy, Richard G. Rahman, Ruman Endothelial-like malignant glioma cells in dynamic three dimensional culture identifies a role for VEGF and FGFR in a tumor-derived angiogenic response |
| title | Endothelial-like malignant glioma cells in dynamic three dimensional culture identifies a role for VEGF and FGFR in a tumor-derived angiogenic response |
| title_full | Endothelial-like malignant glioma cells in dynamic three dimensional culture identifies a role for VEGF and FGFR in a tumor-derived angiogenic response |
| title_fullStr | Endothelial-like malignant glioma cells in dynamic three dimensional culture identifies a role for VEGF and FGFR in a tumor-derived angiogenic response |
| title_full_unstemmed | Endothelial-like malignant glioma cells in dynamic three dimensional culture identifies a role for VEGF and FGFR in a tumor-derived angiogenic response |
| title_short | Endothelial-like malignant glioma cells in dynamic three dimensional culture identifies a role for VEGF and FGFR in a tumor-derived angiogenic response |
| title_sort | endothelial-like malignant glioma cells in dynamic three dimensional culture identifies a role for vegf and fgfr in a tumor-derived angiogenic response |
| topic | vasculogenic mimicry rotary cell culture system angiogenesis glioma tumor-derived endothelium |
| url | https://eprints.nottingham.ac.uk/31768/ https://eprints.nottingham.ac.uk/31768/ https://eprints.nottingham.ac.uk/31768/ |