Angiogenesis, tumor cell proliferation, and migration are the hallmarks of solid tumors, such as gliomas. Recent study has shown that modified COOH-terminal PF4 peptide containing the sequence DLR (PF4-DLR) inhibits endothelial cell proliferation, migration, and microvessel assembly. Systemic administration of PF4-DLR to human glioma models in nude mice resulted in a significant inhibition of tumor growth. No data are available on the molecular determinants associated with the therapeutic response. Proteomics is a powerful technique which allows to identified group of pro- teins which expression change or is associated to treatment. In this study, we have used two-dimensional electrophoresis and mass spectrometry to directly analyze protein profile changes in gliomas during PF4-DLR treat- ment. Nude mice were intracranially inoculated with 50,000 U87 cells and implanted two weeks later with an osmotic minipump filled with PBS or 0.5 mg of PF4-DLR. Mice were sacrificed 10 and 20 days later, and protein analysis was performed by comparing at least seven 2-D SDS gels from each treatment group. Thirty-seven significant spots have been analyzed by mass spectrometry, resulting in the identification of 28 proteins significantly upregulated and 9 proteins significantly downregulated after PF4-DLR treatment. Only three identified proteins originated from the mouse hosttissue. Among all the tumor-derived proteins, 12 proteins seemed corre- lated to the tumor growth-inhibitory effect of PF4-DLR treatment, at both 10 and 20 days of treatment. At 20 days of treatment, 13 proteins seemed correlated to the presence of a subset of tumor cells undergoing to therapy escape growth. We have also found 4 proteins expressed only in the PF4- DLR–treated tumors. Interestingly, one of these proteins, the procollagen C-endopeptidase enhancer 1 precursor (PCPE) has a metalloproteinase- inhibitory activity. In conclusion, the proteins identified by 2-DGE analysis may aid comprehension of PF4-DLR molecular targets
Proteomic analysis of gliomas during Pf4 – dlr antiangiogenesis treatment / C. Verpelli, G. Piccoli, V. Lucini, F. Colleoni, A. Bikfalvi, C. Sala, L. Bello - In: neuro-oncology[s.l] : oxford, 2006.
Proteomic analysis of gliomas during Pf4 – dlr antiangiogenesis treatment
L. Bello
2006
Abstract
Angiogenesis, tumor cell proliferation, and migration are the hallmarks of solid tumors, such as gliomas. Recent study has shown that modified COOH-terminal PF4 peptide containing the sequence DLR (PF4-DLR) inhibits endothelial cell proliferation, migration, and microvessel assembly. Systemic administration of PF4-DLR to human glioma models in nude mice resulted in a significant inhibition of tumor growth. No data are available on the molecular determinants associated with the therapeutic response. Proteomics is a powerful technique which allows to identified group of pro- teins which expression change or is associated to treatment. In this study, we have used two-dimensional electrophoresis and mass spectrometry to directly analyze protein profile changes in gliomas during PF4-DLR treat- ment. Nude mice were intracranially inoculated with 50,000 U87 cells and implanted two weeks later with an osmotic minipump filled with PBS or 0.5 mg of PF4-DLR. Mice were sacrificed 10 and 20 days later, and protein analysis was performed by comparing at least seven 2-D SDS gels from each treatment group. Thirty-seven significant spots have been analyzed by mass spectrometry, resulting in the identification of 28 proteins significantly upregulated and 9 proteins significantly downregulated after PF4-DLR treatment. Only three identified proteins originated from the mouse hosttissue. Among all the tumor-derived proteins, 12 proteins seemed corre- lated to the tumor growth-inhibitory effect of PF4-DLR treatment, at both 10 and 20 days of treatment. At 20 days of treatment, 13 proteins seemed correlated to the presence of a subset of tumor cells undergoing to therapy escape growth. We have also found 4 proteins expressed only in the PF4- DLR–treated tumors. Interestingly, one of these proteins, the procollagen C-endopeptidase enhancer 1 precursor (PCPE) has a metalloproteinase- inhibitory activity. In conclusion, the proteins identified by 2-DGE analysis may aid comprehension of PF4-DLR molecular targetsPubblicazioni consigliate
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