title: Effect of lung squamous cell carcinoma tumor microenvironment on the CD105+ endothelial cell proteome.
abstract: 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.
authors.affiliation: Central Laboratory, The Affiliated Zhongshan Hospital, Xiamen University , Xiamen, Fujian 361004, China.
authors.forename: Huiqin
authors.initials: H
authors.lastname: Zhuo
authors.forename: Zhi
authors.initials: Z
authors.lastname: Lyu
authors.forename: Jing
authors.initials: J
authors.lastname: Su
authors.forename: Jian
authors.initials: J
authors.lastname: He
authors.forename: Yihua
authors.initials: Y
authors.lastname: Pei
authors.forename: Xiao
authors.initials: X
authors.lastname: Cheng
authors.forename: Nuo
authors.initials: N
authors.lastname: Zhou
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Lu
authors.forename: Sufang
authors.initials: S
authors.lastname: Zhou
authors.forename: Yongxiang
authors.initials: Y
authors.lastname: Zhao
mesh_terms: D015703:Antigens, CD / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism*; D002852:Chromatography, Ion Exchange; D002853:Chromatography, Liquid; D019295:Computational Biology; D000071063:Endoglin; D042783:Endothelial Cells / Q000378:metabolism*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D007553:Isotope Labeling; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism*; D020543:Proteome / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D011956:Receptors, Cell Surface / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053719:Tandem Mass Spectrometry; D059016:Tumor Microenvironment / Q000502:physiology*
chemical_list: D015703:Antigens, CD; C064206:ENG protein, human; D000071063:Endoglin; D020543:Proteome; D011956:Receptors, Cell Surface
keywords: iTRAQ; lung squamous cell carcinoma; paratumor endothelial cells; proteomics; tumor endothelial cells