Effect of Lung Squamous Cell Carcinoma Tumor Microenvironment on the CD105+ Endothelial Cell Proteome

In lung cancer, antiangiogenic treatment targeting tumor endothelial cells (ECs) provides a survival advantage. To fully elucidate the behavior of ECs in a tumor microenvironment, high-purity (>98%) normal, paratumor-, and tumor-derived CD105+ ECs were purified from lung squamous cell carcinoma b...

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Veröffentlicht in:Journal of proteome research 2014-11, Vol.13 (11), p.4717-4729
Hauptverfasser: Zhuo, Huiqin, Lyu, Zhi, Su, Jing, He, Jian, Pei, Yihua, Cheng, Xiao, Zhou, Nuo, Lu, Xiaoling, Zhou, Sufang, Zhao, Yongxiang
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container_end_page 4729
container_issue 11
container_start_page 4717
container_title Journal of proteome research
container_volume 13
creator Zhuo, Huiqin
Lyu, Zhi
Su, Jing
He, Jian
Pei, Yihua
Cheng, Xiao
Zhou, Nuo
Lu, Xiaoling
Zhou, Sufang
Zhao, Yongxiang
description In lung cancer, antiangiogenic treatment targeting tumor endothelial cells (ECs) provides a survival advantage. To fully elucidate the behavior of ECs in a tumor microenvironment, high-purity (>98%) normal, paratumor-, and tumor-derived CD105+ ECs were purified from lung squamous cell carcinoma by incubating cells with anti-CD105 antibody-coated magnetic beads. These cells exhibited typical EC characteristics. Totally, 1765 proteins were identified with high confidence by isobaric stable isotope tags and two-dimensional LC/MS/MS (iTRAQ-2DLC/MS/MS). In particular, 178 and 162 proteins were differentially expressed in paratumor- and tumor-derived ECs, respectively, compared to normal ECs. The up- and down-regulation trends showed good interassay correlation. Using gene ontology, they were classified into genes involved in major reprogramming of cellular metabolic processes, oxidative stress response, redox homeostasis, apoptosis, and platelet degranulation/activation. Moreover, tumor angiogenesis-initiating ECs appeared to acquire distinct properties. For example, cell migration and regulation of smooth muscle cell migration of paratumor-derived ECs were significantly faster than that of normal and tumor-derived ECs. Among them, two migration-associated proteins, neuropilin 1 and platelet-derived growth factor receptor β predominantly expressed in ECs of paratumor from 16 patients with lung squamous cell carcinoma, were identified as potential biomarkers for antiangiogenic therapy.
doi_str_mv 10.1021/pr5006229
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Using gene ontology, they were classified into genes involved in major reprogramming of cellular metabolic processes, oxidative stress response, redox homeostasis, apoptosis, and platelet degranulation/activation. Moreover, tumor angiogenesis-initiating ECs appeared to acquire distinct properties. For example, cell migration and regulation of smooth muscle cell migration of paratumor-derived ECs were significantly faster than that of normal and tumor-derived ECs. 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subjects Antigens, CD - metabolism
Carcinoma, Squamous Cell - genetics
Carcinoma, Squamous Cell - metabolism
Chromatography, Ion Exchange
Chromatography, Liquid
Computational Biology
Endoglin
Endothelial Cells - metabolism
Flow Cytometry
Fluorescent Antibody Technique
Gene Expression Regulation, Neoplastic - genetics
Gene Expression Regulation, Neoplastic - physiology
Humans
Immunohistochemistry
Isotope Labeling
Lung Neoplasms - genetics
Lung Neoplasms - metabolism
Proteome - metabolism
Real-Time Polymerase Chain Reaction
Receptors, Cell Surface - metabolism
Reverse Transcriptase Polymerase Chain Reaction
Tandem Mass Spectrometry
Tumor Microenvironment - physiology
title Effect of Lung Squamous Cell Carcinoma Tumor Microenvironment on the CD105+ Endothelial Cell Proteome
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