A proteome comparison between physiological angiogenesis and angiogenesis in glioblastoma.
ABSTRACT The molecular pathways involved in neovascularization of regenerating tissues and tumor angiogenesis resemble each other. However, the regulatory mechanisms of neovascularization under neoplastic circumstances are unbalanced leading to abnormal protein expression patterns resulting in the formation of defective and often abortive tumor vessels. Because gliomas are among the most vascularized tumors, we compared the protein expression profiles of proliferating vessels in glioblastoma with those in tissues in which physiological angiogenesis takes place. By using a combination of laser microdissection and LTQ Orbitrap mass spectrometry comparisons of protein profiles were made. The approach yielded 29 and 12 differentially expressed proteins for glioblastoma and endometrium blood vessels, respectively. The aberrant expression of five proteins, i.e. periostin, tenascin-C, TGF-beta induced protein, integrin alpha-V, and laminin subunit beta-2 were validated by immunohistochemistry. In addition, pathway analysis of the differentially expressed proteins was performed and significant differences in the usage of angiogenic pathways were found. We conclude that there are essential differences in protein expression profiles between tumor and normal physiological angiogenesis.
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ABSTRACT: The identification of differences in vascular architecture and utilization of angiogenic pathways is a first step for identifying specific targets for tailored antiangiogenic therapies of brain tumor patients. Here, we compared the proliferating vasculature of 2 glioma subtypes with entirely different biologic behaviors and molecular background at the immunophenotype and gene expression levels. Proliferating vessels in 13 pilocytic astrocytomas and 8 glioblastomas were compared for differences in the composition of the vascular walls using confocal microscopy for markers of endothelial cells and pericytes/mural cells. Endothelial, pericytic, and mural cells had normal-appearing arrangements in the vessels in pilocytic astrocytomas, whereas those in glioblastomas appeared to be more disorganized. In addition, differences in expression of angiogenesis-related genes were sought in the tumor specimens using RNA expression arrays. There were 114 out of 2,894 differentially expressed angiogenesis-related genes between these 2 glioma subtypes indicating differences in the utilization of various pathways. These results point to the need for detailed information on mechanisms of neoangiogenesis in tumor subtypes to facilitate the development of specific antiangiogenic strategies.Journal of neuropathology and experimental neurology. 11/2013;
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ABSTRACT: Candidate protein biomarker discovery by full automatic integration of Orbitrap full MS1 spectral peptide profiling and X!Tandem MS2 peptide sequencing is investigated by analyzing mass spectra from brain tumor samples using Peptrix. Potential protein candidate biomarkers found for angiogenesis are compared with those previously reported in literature and obtained from previous Fourier transform ion cyclotron resonance (FT-ICR) peptide profiling. Lower mass accuracy of peptide masses measured by Orbitrap compared to those measured by FT-ICR is compensated by the larger number of detected masses separated by liquid chromatography (LC), which can be directly linked to protein identifications. The number of peptide sequences divided by the number of unique sequences is 9248/6911 ≈ 1.3. Peptide sequences appear 1.3 times redundant per up-regulated protein on average in the peptide profile matrix, and don't seem always up-regulated due to tailing in LC retention time (40%), modifications (40%) and mass determination errors (20%). Significantly up-regulated proteins found by integration of X!Tandem are described in literature as tumor markers and some are linked to angiogenesis. New potential biomarkers are found, but need to be validated independently. Eventually more proteins could be found by actively involving MS2 sequence information in the creation of the MS1 peptide profile matrix.Genomics Proteomics & Bioinformatics 04/2013;
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ABSTRACT: Despite detailed knowledge about the structure and signaling properties of individual collagen receptors, much remains to be learned about how these receptors participate in linking cells to fibrillar collagen matrices in tissues. In addition to collagen-binding integrins, a group of proteins with affinity both for fibrillar collagens and integrins link these two protein families together. We have introduced the name COLINBRI (COLlagen INtegrin BRIdging molecules) for this set of molecules. Whereas collagens are the major building blocks in tissues, defects in these structural proteins have severe consequences for tissue integrity; the mild phenotypes of the integrin type of collagen receptors have raised questions about their importance in tissue biology and pathology. Scope of review We will discuss the two types of cell linkages to fibrillar collagen (direct- versus indirect COLINBRI-mediated) and discuss how the parallel existence of direct and indirect linkages to collagens may ensure tissue integrity. Major conclusions The observed mild phenotypes of mice deficient in collagen-binding integrins and the relatively restricted availability of integrin-binding sequences in mature fibrillar collagens matrices support the existence of indirect collagen binding mechanisms in parallel with direct collagen binding in vivo. General significance A continued focus on understanding the molecular details of cell adhesion mechanisms to collagens will be important and will benefit our understanding of diseases like tissue- and tumor fibrosis where collagen dynamics are disturbed.Biochimica et Biophysica Acta 12/2013; · 4.66 Impact Factor