SILAC-based proteomics of human primary endothelial cell morphogenesis unveils tumor angiogenic markers.

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Because of the complexity of the angiogenic program, we still do not have a complete understanding of the molecular mechanisms involved in this process, and there have been no in depth quantitative proteomic studies. Plating endothelial cells on matrigel recapitulates aspects of vessel growth, and here we investigate this mechanism by using a spike-in SILAC quantitative proteomic approach. By comparing proteomic changes in primary human endothelial cells morphogenesis on matrigel to general adhesion mechanisms in cells spreading on culture dish, we pinpoint pathways and proteins modulated by endothelial cells. The cell-extracellular matrix adhesion proteome depends on the adhesion substrate, and a detailed proteomic profile of the extracellular matrix secreted by endothelial cells identified CLEC14A as a matrix component, which binds to MMRN2. We verify deregulated levels of these proteins during tumor angiogenesis in models of multistage carcinogenesis. This is the most in depth quantitative proteomic study of endothelial cell morphogenesis, which shows the potential of applying high accuracy quantitative proteomics to in vitro models of vessel growth to shed new light on mechanisms that accompany pathological angiogenesis. The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium with the data set identifier PXD000359.", "claims": [{"id": "claim-target-result", "statement": "The paper reports that endothelial-cell morphogenesis is modulated by substrate-dependent cell–extracellular matrix adhesion, identifies CLEC14A as an extracellular matrix component that binds MMRN2, and verifies deregulated levels of these proteins during tumor angiogenesis; it used a spike-in SILAC quantitative proteomic approach, with mass spectrometry data deposited in ProteomeXchange under PXD000359. No specific statistical method is stated in the Abstract.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:23979707", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "By comparing proteomic changes in primary human endothelial cells morphogenesis on matrigel to general adhesion mechanisms in cells spreading on culture dish, we pinpoint pathways and proteins modulated by endothelial cells."}, {"asset": "source:pmid:23979707", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "The cell–extracellular matrix adhesion proteome depends on the adhesion substrate, and a detailed proteomic profile of the extracellular matrix secreted by endothelial cells identified CLEC14A as a matrix component, which binds to MMRN2."}, {"asset": "source:pmid:23979707", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "We verify deregulated levels of these proteins during tumor angiogenesis in models of multistage carcinogenesis."}, {"asset": "source:pmid:23979707", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium with the data set identifier PXD000359."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "The paper reports that endothelial-cell morphogenesis is modulated by substrate-dependent cell–extracellular matrix adhesion, identifies CLEC14A as an extracellular matrix component that binds MMRN2, and verifies deregulated levels of these proteins during tumor angiogenesis; it used a spike-in SILAC quantitative proteomic approach, with mass spectrometry data deposited in ProteomeXchange under PXD000359. 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