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iTRAQ-based Proteomics Profiling Reveals Increased Metabolic Activity and Cellular Cross-talk in Angiogenic Compared with Invasive Glioblastoma Phenotype
Malignant gliomas (glioblastoma multiforme) have a poor prognosis with an average patient survival under current treatment regimens ranging between 12 and 14 months. The tumors are characterized by rapid cell growth, extensive neovascularization, and diffuse cellular infiltration of normal brain str...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
The American Society for Biochemistry and Molecular Biology
2009
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2773724/ https://www.ncbi.nlm.nih.gov/pubmed/19674965 http://dx.doi.org/10.1074/mcp.M900124-MCP200 |
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author | Rajcevic, Uros Petersen, Kjell Knol, Jaco C. Loos, Maarten Bougnaud, Sébastien Klychnikov, Oleg Li, Ka Wan Pham, Thang V. Wang, Jian Miletic, Hrvoje Peng, Zhao Bjerkvig, Rolf Jimenez, Connie R. Niclou, Simone P. |
author_facet | Rajcevic, Uros Petersen, Kjell Knol, Jaco C. Loos, Maarten Bougnaud, Sébastien Klychnikov, Oleg Li, Ka Wan Pham, Thang V. Wang, Jian Miletic, Hrvoje Peng, Zhao Bjerkvig, Rolf Jimenez, Connie R. Niclou, Simone P. |
author_sort | Rajcevic, Uros |
collection | PubMed |
description | Malignant gliomas (glioblastoma multiforme) have a poor prognosis with an average patient survival under current treatment regimens ranging between 12 and 14 months. The tumors are characterized by rapid cell growth, extensive neovascularization, and diffuse cellular infiltration of normal brain structures. We have developed a human glioblastoma xenograft model in nude rats that is characterized by a highly infiltrative non-angiogenic phenotype. Upon serial transplantation this phenotype will develop into a highly angiogenic tumor. Thus, we have developed an animal model where we are able to establish two characteristic tumor phenotypes that define human glioblastoma (i.e. diffuse infiltration and high neovascularization). Here we aimed at identifying potential biomarkers expressed by the non-angiogenic and the angiogenic phenotypes and elucidating the molecular pathways involved in the switch from invasive to angiogenic growth. Focusing on membrane-associated proteins, we profiled protein expression during the progression from an invasive to an angiogenic phenotype by analyzing serially transplanted glioma xenografts in rats. Applying isobaric peptide tagging chemistry (iTRAQ) combined with two-dimensional LC and MALDI-TOF/TOF mass spectrometry, we were able to identify several thousand proteins in membrane-enriched fractions of which 1460 were extracted as quantifiable proteins (isoform- and species-specific and present in more than one sample). Known and novel candidate proteins were identified that characterize the switch from a non-angiogenic to a highly angiogenic phenotype. The robustness of the data was corroborated by extensive bioinformatics analysis and by validation of selected proteins on tissue microarrays from xenograft and clinical gliomas. The data point to enhanced intercellular cross-talk and metabolic activity adopted by tumor cells in the angiogenic compared with the non-angiogenic phenotype. In conclusion, we describe molecular profiles that reflect the change from an invasive to an angiogenic brain tumor phenotype. The identified proteins could be further exploited as biomarkers or therapeutic targets for malignant gliomas. |
format | Text |
id | pubmed-2773724 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | The American Society for Biochemistry and Molecular Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-27737242009-11-06 iTRAQ-based Proteomics Profiling Reveals Increased Metabolic Activity and Cellular Cross-talk in Angiogenic Compared with Invasive Glioblastoma Phenotype Rajcevic, Uros Petersen, Kjell Knol, Jaco C. Loos, Maarten Bougnaud, Sébastien Klychnikov, Oleg Li, Ka Wan Pham, Thang V. Wang, Jian Miletic, Hrvoje Peng, Zhao Bjerkvig, Rolf Jimenez, Connie R. Niclou, Simone P. Mol Cell Proteomics Research Malignant gliomas (glioblastoma multiforme) have a poor prognosis with an average patient survival under current treatment regimens ranging between 12 and 14 months. The tumors are characterized by rapid cell growth, extensive neovascularization, and diffuse cellular infiltration of normal brain structures. We have developed a human glioblastoma xenograft model in nude rats that is characterized by a highly infiltrative non-angiogenic phenotype. Upon serial transplantation this phenotype will develop into a highly angiogenic tumor. Thus, we have developed an animal model where we are able to establish two characteristic tumor phenotypes that define human glioblastoma (i.e. diffuse infiltration and high neovascularization). Here we aimed at identifying potential biomarkers expressed by the non-angiogenic and the angiogenic phenotypes and elucidating the molecular pathways involved in the switch from invasive to angiogenic growth. Focusing on membrane-associated proteins, we profiled protein expression during the progression from an invasive to an angiogenic phenotype by analyzing serially transplanted glioma xenografts in rats. Applying isobaric peptide tagging chemistry (iTRAQ) combined with two-dimensional LC and MALDI-TOF/TOF mass spectrometry, we were able to identify several thousand proteins in membrane-enriched fractions of which 1460 were extracted as quantifiable proteins (isoform- and species-specific and present in more than one sample). Known and novel candidate proteins were identified that characterize the switch from a non-angiogenic to a highly angiogenic phenotype. The robustness of the data was corroborated by extensive bioinformatics analysis and by validation of selected proteins on tissue microarrays from xenograft and clinical gliomas. The data point to enhanced intercellular cross-talk and metabolic activity adopted by tumor cells in the angiogenic compared with the non-angiogenic phenotype. In conclusion, we describe molecular profiles that reflect the change from an invasive to an angiogenic brain tumor phenotype. The identified proteins could be further exploited as biomarkers or therapeutic targets for malignant gliomas. The American Society for Biochemistry and Molecular Biology 2009-11 2009-08-12 /pmc/articles/PMC2773724/ /pubmed/19674965 http://dx.doi.org/10.1074/mcp.M900124-MCP200 Text en © 2009 by The American Society for Biochemistry and Molecular Biology, Inc. Author's Choice—Final version full access. Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) applies to Author Choice Articles |
spellingShingle | Research Rajcevic, Uros Petersen, Kjell Knol, Jaco C. Loos, Maarten Bougnaud, Sébastien Klychnikov, Oleg Li, Ka Wan Pham, Thang V. Wang, Jian Miletic, Hrvoje Peng, Zhao Bjerkvig, Rolf Jimenez, Connie R. Niclou, Simone P. iTRAQ-based Proteomics Profiling Reveals Increased Metabolic Activity and Cellular Cross-talk in Angiogenic Compared with Invasive Glioblastoma Phenotype |
title | iTRAQ-based Proteomics Profiling Reveals Increased Metabolic Activity and Cellular Cross-talk in Angiogenic Compared with Invasive Glioblastoma Phenotype |
title_full | iTRAQ-based Proteomics Profiling Reveals Increased Metabolic Activity and Cellular Cross-talk in Angiogenic Compared with Invasive Glioblastoma Phenotype |
title_fullStr | iTRAQ-based Proteomics Profiling Reveals Increased Metabolic Activity and Cellular Cross-talk in Angiogenic Compared with Invasive Glioblastoma Phenotype |
title_full_unstemmed | iTRAQ-based Proteomics Profiling Reveals Increased Metabolic Activity and Cellular Cross-talk in Angiogenic Compared with Invasive Glioblastoma Phenotype |
title_short | iTRAQ-based Proteomics Profiling Reveals Increased Metabolic Activity and Cellular Cross-talk in Angiogenic Compared with Invasive Glioblastoma Phenotype |
title_sort | itraq-based proteomics profiling reveals increased metabolic activity and cellular cross-talk in angiogenic compared with invasive glioblastoma phenotype |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2773724/ https://www.ncbi.nlm.nih.gov/pubmed/19674965 http://dx.doi.org/10.1074/mcp.M900124-MCP200 |
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