Anti-angiogenic therapy induces integrin-linked kinase 1 up-regulation in a mouse model of glioblastoma.
BACKGROUND: In order to improve our understanding of the molecular pathways that mediate tumor proliferation and angiogenesis, and to evaluate the biological response to anti-angiogenic therapy, we analyzed the changes in the protein profile of glioblastoma in response to treatment with recombinant...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2010-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC2966411?pdf=render |
| _version_ | 1818065628195454976 |
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| author | Chiara Verpelli Giulio Bertani Valentina Cea Monica Patti Andreas Bikfalvi Lorenzo Bello Carlo Sala |
| author_facet | Chiara Verpelli Giulio Bertani Valentina Cea Monica Patti Andreas Bikfalvi Lorenzo Bello Carlo Sala |
| author_sort | Chiara Verpelli |
| collection | DOAJ |
| description | BACKGROUND: In order to improve our understanding of the molecular pathways that mediate tumor proliferation and angiogenesis, and to evaluate the biological response to anti-angiogenic therapy, we analyzed the changes in the protein profile of glioblastoma in response to treatment with recombinant human Platelet Factor 4-DLR mutated protein (PF4-DLR), an inhibitor of angiogenesis. METHODOLOGY/PRINCIPAL FINDINGS: U87-derived experimental glioblastomas were grown in the brain of xenografted nude mice, treated with PF4-DLR, and processed for proteomic analysis. More than fifty proteins were differentially expressed in response to PF4-DLR treatment. Among them, integrin-linked kinase 1 (ILK1) signaling pathway was first down-regulated but then up-regulated after treatment for prolonged period. The activity of PF4-DLR can be increased by simultaneously treating mice orthotopically implanted with glioblastomas, with ILK1-specific siRNA. As ILK1 is related to malignant progression and a poor prognosis in various types of tumors, we measured ILK1 expression in human glioblastomas, astrocytomas and oligodendrogliomas, and found that it varied widely; however, a high level of ILK1 expression was correlated to a poor prognosis. CONCLUSIONS/SIGNIFICANCE: Our results suggest that identifying the molecular pathways induced by anti-angiogenic therapies may help the development of combinatorial treatment strategies that increase the therapeutic efficacy of angiogenesis inhibitors by association with specific agents that disrupt signaling in tumor cells. |
| first_indexed | 2024-12-10T14:54:55Z |
| format | Article |
| id | doaj.art-a2db0ceb77b04f61a93c5825529519dc |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-10T14:54:55Z |
| publishDate | 2010-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-a2db0ceb77b04f61a93c5825529519dc2022-12-22T01:44:21ZengPublic Library of Science (PLoS)PLoS ONE1932-62032010-01-01510e1371010.1371/journal.pone.0013710Anti-angiogenic therapy induces integrin-linked kinase 1 up-regulation in a mouse model of glioblastoma.Chiara VerpelliGiulio BertaniValentina CeaMonica PattiAndreas BikfalviLorenzo BelloCarlo SalaBACKGROUND: In order to improve our understanding of the molecular pathways that mediate tumor proliferation and angiogenesis, and to evaluate the biological response to anti-angiogenic therapy, we analyzed the changes in the protein profile of glioblastoma in response to treatment with recombinant human Platelet Factor 4-DLR mutated protein (PF4-DLR), an inhibitor of angiogenesis. METHODOLOGY/PRINCIPAL FINDINGS: U87-derived experimental glioblastomas were grown in the brain of xenografted nude mice, treated with PF4-DLR, and processed for proteomic analysis. More than fifty proteins were differentially expressed in response to PF4-DLR treatment. Among them, integrin-linked kinase 1 (ILK1) signaling pathway was first down-regulated but then up-regulated after treatment for prolonged period. The activity of PF4-DLR can be increased by simultaneously treating mice orthotopically implanted with glioblastomas, with ILK1-specific siRNA. As ILK1 is related to malignant progression and a poor prognosis in various types of tumors, we measured ILK1 expression in human glioblastomas, astrocytomas and oligodendrogliomas, and found that it varied widely; however, a high level of ILK1 expression was correlated to a poor prognosis. CONCLUSIONS/SIGNIFICANCE: Our results suggest that identifying the molecular pathways induced by anti-angiogenic therapies may help the development of combinatorial treatment strategies that increase the therapeutic efficacy of angiogenesis inhibitors by association with specific agents that disrupt signaling in tumor cells.http://europepmc.org/articles/PMC2966411?pdf=render |
| spellingShingle | Chiara Verpelli Giulio Bertani Valentina Cea Monica Patti Andreas Bikfalvi Lorenzo Bello Carlo Sala Anti-angiogenic therapy induces integrin-linked kinase 1 up-regulation in a mouse model of glioblastoma. PLoS ONE |
| title | Anti-angiogenic therapy induces integrin-linked kinase 1 up-regulation in a mouse model of glioblastoma. |
| title_full | Anti-angiogenic therapy induces integrin-linked kinase 1 up-regulation in a mouse model of glioblastoma. |
| title_fullStr | Anti-angiogenic therapy induces integrin-linked kinase 1 up-regulation in a mouse model of glioblastoma. |
| title_full_unstemmed | Anti-angiogenic therapy induces integrin-linked kinase 1 up-regulation in a mouse model of glioblastoma. |
| title_short | Anti-angiogenic therapy induces integrin-linked kinase 1 up-regulation in a mouse model of glioblastoma. |
| title_sort | anti angiogenic therapy induces integrin linked kinase 1 up regulation in a mouse model of glioblastoma |
| url | http://europepmc.org/articles/PMC2966411?pdf=render |
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