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 |
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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. |
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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.</description><identifier>ISSN: 1535-3893</identifier><identifier>EISSN: 1535-3907</identifier><identifier>DOI: 10.1021/pr5006229</identifier><identifier>PMID: 25238122</identifier><language>eng</language><publisher>United States: American Chemical Society</publisher><subject>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</subject><ispartof>Journal of proteome research, 2014-11, Vol.13 (11), p.4717-4729</ispartof><rights>Copyright © 2014 American Chemical Society</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a315t-387d37ce41a27875f22d1a40fc95f3cbe6eb9e1d9dcfed92e0ff4160917070cf3</citedby><cites>FETCH-LOGICAL-a315t-387d37ce41a27875f22d1a40fc95f3cbe6eb9e1d9dcfed92e0ff4160917070cf3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/pr5006229$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/pr5006229$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>314,778,782,2754,27065,27913,27914,56727,56777</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25238122$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhuo, Huiqin</creatorcontrib><creatorcontrib>Lyu, Zhi</creatorcontrib><creatorcontrib>Su, Jing</creatorcontrib><creatorcontrib>He, Jian</creatorcontrib><creatorcontrib>Pei, Yihua</creatorcontrib><creatorcontrib>Cheng, Xiao</creatorcontrib><creatorcontrib>Zhou, Nuo</creatorcontrib><creatorcontrib>Lu, Xiaoling</creatorcontrib><creatorcontrib>Zhou, Sufang</creatorcontrib><creatorcontrib>Zhao, Yongxiang</creatorcontrib><title>Effect of Lung Squamous Cell Carcinoma Tumor Microenvironment on the CD105+ Endothelial Cell Proteome</title><title>Journal of proteome research</title><addtitle>J. Proteome Res</addtitle><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.</description><subject>Antigens, CD - metabolism</subject><subject>Carcinoma, Squamous Cell - genetics</subject><subject>Carcinoma, Squamous Cell - metabolism</subject><subject>Chromatography, Ion Exchange</subject><subject>Chromatography, Liquid</subject><subject>Computational Biology</subject><subject>Endoglin</subject><subject>Endothelial Cells - metabolism</subject><subject>Flow Cytometry</subject><subject>Fluorescent Antibody Technique</subject><subject>Gene Expression Regulation, Neoplastic - genetics</subject><subject>Gene Expression Regulation, Neoplastic - physiology</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Isotope Labeling</subject><subject>Lung Neoplasms - genetics</subject><subject>Lung Neoplasms - metabolism</subject><subject>Proteome - metabolism</subject><subject>Real-Time Polymerase Chain Reaction</subject><subject>Receptors, Cell Surface - metabolism</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>Tandem Mass Spectrometry</subject><subject>Tumor Microenvironment - physiology</subject><issn>1535-3893</issn><issn>1535-3907</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNptkEtLAzEUhYMotlYX_gHJRlCkmsek0yxlrA-oKFjXQ5q50SmTpE1mBP-9kaldubr3wncO9xyETim5poTRm3UQhEwYk3toSAUXYy5Jvv-3TyUfoKMYV4RQkRN-iAZMMD6ljA0RzIwB3WJv8LxzH_ht0ynru4gLaBpcqKBr563Ci876gJ9rHTy4rzp4Z8ElmcPtJ-DijhJxhWeu8ulsatX0-tfgW_AWjtGBUU2Ek-0coff72aJ4HM9fHp6K2_lYcSra9Gpe8VxDRhXLp7kwjFVUZcRoKQzXS5jAUgKtZKUNVJIBMSajEyJpTnKiDR-hi953Hfymg9iWto46faIcpFAlTSWRiaCZSOhlj6ZEMQYw5TrUVoXvkpLyt9Vy12piz7a23dJCtSP_akzAeQ8oHcuV74JLKf8x-gHQJX0y</recordid><startdate>20141107</startdate><enddate>20141107</enddate><creator>Zhuo, Huiqin</creator><creator>Lyu, Zhi</creator><creator>Su, Jing</creator><creator>He, Jian</creator><creator>Pei, Yihua</creator><creator>Cheng, Xiao</creator><creator>Zhou, Nuo</creator><creator>Lu, Xiaoling</creator><creator>Zhou, Sufang</creator><creator>Zhao, Yongxiang</creator><general>American Chemical Society</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20141107</creationdate><title>Effect of Lung Squamous Cell Carcinoma Tumor Microenvironment on the CD105+ Endothelial Cell Proteome</title><author>Zhuo, Huiqin ; Lyu, Zhi ; Su, Jing ; He, Jian ; Pei, Yihua ; Cheng, Xiao ; Zhou, Nuo ; Lu, Xiaoling ; Zhou, Sufang ; Zhao, Yongxiang</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a315t-387d37ce41a27875f22d1a40fc95f3cbe6eb9e1d9dcfed92e0ff4160917070cf3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Antigens, CD - metabolism</topic><topic>Carcinoma, Squamous Cell - genetics</topic><topic>Carcinoma, Squamous Cell - metabolism</topic><topic>Chromatography, Ion Exchange</topic><topic>Chromatography, Liquid</topic><topic>Computational Biology</topic><topic>Endoglin</topic><topic>Endothelial Cells - metabolism</topic><topic>Flow Cytometry</topic><topic>Fluorescent Antibody Technique</topic><topic>Gene Expression Regulation, Neoplastic - genetics</topic><topic>Gene Expression Regulation, Neoplastic - physiology</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Isotope Labeling</topic><topic>Lung Neoplasms - genetics</topic><topic>Lung Neoplasms - metabolism</topic><topic>Proteome - metabolism</topic><topic>Real-Time Polymerase Chain Reaction</topic><topic>Receptors, Cell Surface - metabolism</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>Tandem Mass Spectrometry</topic><topic>Tumor Microenvironment - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhuo, Huiqin</creatorcontrib><creatorcontrib>Lyu, Zhi</creatorcontrib><creatorcontrib>Su, Jing</creatorcontrib><creatorcontrib>He, Jian</creatorcontrib><creatorcontrib>Pei, Yihua</creatorcontrib><creatorcontrib>Cheng, Xiao</creatorcontrib><creatorcontrib>Zhou, Nuo</creatorcontrib><creatorcontrib>Lu, Xiaoling</creatorcontrib><creatorcontrib>Zhou, Sufang</creatorcontrib><creatorcontrib>Zhao, Yongxiang</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of proteome research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhuo, Huiqin</au><au>Lyu, Zhi</au><au>Su, Jing</au><au>He, Jian</au><au>Pei, Yihua</au><au>Cheng, Xiao</au><au>Zhou, Nuo</au><au>Lu, Xiaoling</au><au>Zhou, Sufang</au><au>Zhao, Yongxiang</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effect of Lung Squamous Cell Carcinoma Tumor Microenvironment on the CD105+ Endothelial Cell Proteome</atitle><jtitle>Journal of proteome research</jtitle><addtitle>J. Proteome Res</addtitle><date>2014-11-07</date><risdate>2014</risdate><volume>13</volume><issue>11</issue><spage>4717</spage><epage>4729</epage><pages>4717-4729</pages><issn>1535-3893</issn><eissn>1535-3907</eissn><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. 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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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