Interleukin-8/CXCL8 is a growth factor for human lung cancer cells
Interleukin-8/CXCL8 (IL-8) is a chemokine and angiogenic factor. Recently, IL-8 was identified as an autocrine growth factor in several human cancers. Here, we investigated the expression and function of IL-8 in lung cancer cells. The expressions of IL-8 and its receptors, CXCR1 and CXCR2, were exam...
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| Veröffentlicht in: | British journal of cancer 2004-11, Vol.91 (11), p.1970-1976 |
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| creator | Zhu, Y M Webster, S J Flower, D Woll, P J |
| description | Interleukin-8/CXCL8 (IL-8) is a chemokine and angiogenic factor. Recently, IL-8 was identified as an autocrine growth factor in several human cancers. Here, we investigated the expression and function of IL-8 in lung cancer cells. The expressions of IL-8 and its receptors, CXCR1 and CXCR2, were examined in a panel of non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) cell lines. Using reverse transcription–polymerase chain reaction (RT–PCR) and enzyme-linked immunosorbent assay, we found that all NSCLC cell lines tested produced modest or high levels of IL-8 (up to 51 ng ml
−1
10
6
cells
−1
). Expression of CXCR1 and CXCR2 was found by RT–PCR and flow cytometry in two out of three cell lines. In contrast, SCLC cell lines produced very low or undetectable levels of IL-8, but expressed CXCR1 and CXCR2. We next investigated whether IL-8 could act as an autocrine growth factor in two NSCLC cell lines (H460 and MOR/P) expressing both IL-8 and its receptors. We found that cell proliferation was attenuated by anti-IL-8 neutralising antibody to 71 and 76% in H460 and MOR/P, respectively (
P |
| doi_str_mv | 10.1038/sj.bjc.6602227 |
| format | Article |
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−1
10
6
cells
−1
). Expression of CXCR1 and CXCR2 was found by RT–PCR and flow cytometry in two out of three cell lines. In contrast, SCLC cell lines produced very low or undetectable levels of IL-8, but expressed CXCR1 and CXCR2. We next investigated whether IL-8 could act as an autocrine growth factor in two NSCLC cell lines (H460 and MOR/P) expressing both IL-8 and its receptors. We found that cell proliferation was attenuated by anti-IL-8 neutralising antibody to 71 and 76% in H460 and MOR/P, respectively (
P
<0.05). Exogenous IL-8 significantly stimulated cell proliferation in four SCLC cell lines tested in a dose-dependent fashion. Cell proliferation was increased by between 18% (
P
<0.05) and 37% (
P
<0.05). Stimulation of cell proliferation by IL-8 was also demonstrated by analysis of proliferating cell nuclear antigen expression and cell cycle in H69 cells. Furthermore, we investigated which receptor(s) mediated the mitogenic function of IL-8 in lung cancer cells. We found that cell proliferation was significantly reduced by anti-CXCR1 antibody but not by anti-CXCR2 antibody. In conclusion, IL-8 can act as an autocrine and/or paracrine growth factor for lung cancer cells, and the mitogenic function of IL-8 in lung cancer is mediated mainly by CXCR1 receptor.</description><identifier>ISSN: 0007-0920</identifier><identifier>EISSN: 1532-1827</identifier><identifier>DOI: 10.1038/sj.bjc.6602227</identifier><identifier>PMID: 15545974</identifier><identifier>CODEN: BJCAAI</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>Autocrine Communication ; Biological and medical sciences ; Biomedical and Life Sciences ; Biomedicine ; Cancer Research ; Carcinoma, Non-Small-Cell Lung - genetics ; Carcinoma, Non-Small-Cell Lung - metabolism ; Carcinoma, Small Cell - genetics ; Carcinoma, Small Cell - metabolism ; Cell Proliferation ; Drug Resistance ; Enzyme-Linked Immunosorbent Assay ; Epidemiology ; Experimental Therapeutics ; Flow Cytometry ; Humans ; Interleukin-8 - metabolism ; Lung cancer ; Lung Neoplasms - genetics ; Lung Neoplasms - metabolism ; Medical sciences ; Molecular Medicine ; Oncology ; Paracrine Communication ; Pneumology ; Receptors, Interleukin-8A - genetics ; Receptors, Interleukin-8A - metabolism ; Receptors, Interleukin-8B - genetics ; Receptors, Interleukin-8B - metabolism ; Recombinant Proteins - isolation & purification ; Recombinant Proteins - metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; RNA, Neoplasm - genetics ; RNA, Neoplasm - metabolism ; Transfection ; Tumor Cells, Cultured ; Tumors ; Tumors of the respiratory system and mediastinum</subject><ispartof>British journal of cancer, 2004-11, Vol.91 (11), p.1970-1976</ispartof><rights>The Author(s) 2004</rights><rights>2005 INIST-CNRS</rights><rights>Copyright Nature Publishing Group Nov 29, 2004</rights><rights>Copyright © 2004 Cancer Research UK 2004 Cancer Research UK</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c516t-a6f9038b5c871bf162e397cc44b193dd10b4740c2112c177704e9f5b305d42e53</citedby><cites>FETCH-LOGICAL-c516t-a6f9038b5c871bf162e397cc44b193dd10b4740c2112c177704e9f5b305d42e53</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2409768/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2409768/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,41464,42533,51294,53766,53768</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=16336458$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15545974$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhu, Y M</creatorcontrib><creatorcontrib>Webster, S J</creatorcontrib><creatorcontrib>Flower, D</creatorcontrib><creatorcontrib>Woll, P J</creatorcontrib><title>Interleukin-8/CXCL8 is a growth factor for human lung cancer cells</title><title>British journal of cancer</title><addtitle>Br J Cancer</addtitle><addtitle>Br J Cancer</addtitle><description>Interleukin-8/CXCL8 (IL-8) is a chemokine and angiogenic factor. Recently, IL-8 was identified as an autocrine growth factor in several human cancers. Here, we investigated the expression and function of IL-8 in lung cancer cells. The expressions of IL-8 and its receptors, CXCR1 and CXCR2, were examined in a panel of non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) cell lines. Using reverse transcription–polymerase chain reaction (RT–PCR) and enzyme-linked immunosorbent assay, we found that all NSCLC cell lines tested produced modest or high levels of IL-8 (up to 51 ng ml
−1
10
6
cells
−1
). Expression of CXCR1 and CXCR2 was found by RT–PCR and flow cytometry in two out of three cell lines. In contrast, SCLC cell lines produced very low or undetectable levels of IL-8, but expressed CXCR1 and CXCR2. We next investigated whether IL-8 could act as an autocrine growth factor in two NSCLC cell lines (H460 and MOR/P) expressing both IL-8 and its receptors. We found that cell proliferation was attenuated by anti-IL-8 neutralising antibody to 71 and 76% in H460 and MOR/P, respectively (
P
<0.05). Exogenous IL-8 significantly stimulated cell proliferation in four SCLC cell lines tested in a dose-dependent fashion. Cell proliferation was increased by between 18% (
P
<0.05) and 37% (
P
<0.05). Stimulation of cell proliferation by IL-8 was also demonstrated by analysis of proliferating cell nuclear antigen expression and cell cycle in H69 cells. Furthermore, we investigated which receptor(s) mediated the mitogenic function of IL-8 in lung cancer cells. We found that cell proliferation was significantly reduced by anti-CXCR1 antibody but not by anti-CXCR2 antibody. In conclusion, IL-8 can act as an autocrine and/or paracrine growth factor for lung cancer cells, and the mitogenic function of IL-8 in lung cancer is mediated mainly by CXCR1 receptor.</description><subject>Autocrine Communication</subject><subject>Biological and medical sciences</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cancer Research</subject><subject>Carcinoma, Non-Small-Cell Lung - genetics</subject><subject>Carcinoma, Non-Small-Cell Lung - metabolism</subject><subject>Carcinoma, Small Cell - genetics</subject><subject>Carcinoma, Small Cell - metabolism</subject><subject>Cell Proliferation</subject><subject>Drug Resistance</subject><subject>Enzyme-Linked Immunosorbent Assay</subject><subject>Epidemiology</subject><subject>Experimental Therapeutics</subject><subject>Flow Cytometry</subject><subject>Humans</subject><subject>Interleukin-8 - metabolism</subject><subject>Lung cancer</subject><subject>Lung Neoplasms - genetics</subject><subject>Lung Neoplasms - metabolism</subject><subject>Medical sciences</subject><subject>Molecular Medicine</subject><subject>Oncology</subject><subject>Paracrine Communication</subject><subject>Pneumology</subject><subject>Receptors, Interleukin-8A - genetics</subject><subject>Receptors, Interleukin-8A - metabolism</subject><subject>Receptors, Interleukin-8B - genetics</subject><subject>Receptors, Interleukin-8B - metabolism</subject><subject>Recombinant Proteins - isolation & purification</subject><subject>Recombinant Proteins - metabolism</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Messenger - metabolism</subject><subject>RNA, Neoplasm - genetics</subject><subject>RNA, Neoplasm - metabolism</subject><subject>Transfection</subject><subject>Tumor Cells, Cultured</subject><subject>Tumors</subject><subject>Tumors of the respiratory system and mediastinum</subject><issn>0007-0920</issn><issn>1532-1827</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNqFkc1LJDEQxYMoOqtePUojuLeeqXx3Lgs67IcwsBcFbyGdSc9025PWpFvZ_34zTLPjCsseQgj1y6t69RC6wDDFQItZbKZlY6dCACFEHqAJ5pTkuCDyEE0AQOagCJygTzE26amgkMfoBHPOuJJsgm7vfO9C64an2ufFbP44XxRZHTOTrUL31q-zyti-C1mVznrYGJ-1g19l1njrQmZd28YzdFSZNrrz8T5FD9--3s9_5Iuf3-_mN4vcciz63IhKpYlLbguJywoL4qiS1jJWYkWXSwwlkwwswZhYLKUE5lTFSwp8yYjj9BR92ek-D-XGLa3zfTCtfg71xoRfujO1_rvi67Veda-aMFBSFEng8ygQupfBxV5v6ri1YLzrhqiFBKUk_T-IJQUmqUrg1Qew6Ybg0xY0odvts0IkaLqDbOhiDK76MzIGvQ1Rx0anEPUYYvpw-d7oHh9TS8D1CJhoTVuFlEYd95ygVDC-9THbcTGV_MqF_Xj_aP0bJpSzYA</recordid><startdate>20041129</startdate><enddate>20041129</enddate><creator>Zhu, Y M</creator><creator>Webster, S J</creator><creator>Flower, D</creator><creator>Woll, P J</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>C6C</scope><scope>IQODW</scope><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>3V.</scope><scope>7RV</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AN0</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20041129</creationdate><title>Interleukin-8/CXCL8 is a growth factor for human lung cancer cells</title><author>Zhu, Y M ; Webster, S J ; Flower, D ; Woll, P J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c516t-a6f9038b5c871bf162e397cc44b193dd10b4740c2112c177704e9f5b305d42e53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Autocrine Communication</topic><topic>Biological and medical sciences</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Cancer Research</topic><topic>Carcinoma, Non-Small-Cell Lung - genetics</topic><topic>Carcinoma, Non-Small-Cell Lung - metabolism</topic><topic>Carcinoma, Small Cell - genetics</topic><topic>Carcinoma, Small Cell - metabolism</topic><topic>Cell Proliferation</topic><topic>Drug Resistance</topic><topic>Enzyme-Linked Immunosorbent Assay</topic><topic>Epidemiology</topic><topic>Experimental Therapeutics</topic><topic>Flow Cytometry</topic><topic>Humans</topic><topic>Interleukin-8 - metabolism</topic><topic>Lung cancer</topic><topic>Lung Neoplasms - genetics</topic><topic>Lung Neoplasms - metabolism</topic><topic>Medical sciences</topic><topic>Molecular Medicine</topic><topic>Oncology</topic><topic>Paracrine Communication</topic><topic>Pneumology</topic><topic>Receptors, Interleukin-8A - genetics</topic><topic>Receptors, Interleukin-8A - metabolism</topic><topic>Receptors, Interleukin-8B - genetics</topic><topic>Receptors, Interleukin-8B - metabolism</topic><topic>Recombinant Proteins - isolation & purification</topic><topic>Recombinant Proteins - metabolism</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Messenger - metabolism</topic><topic>RNA, Neoplasm - genetics</topic><topic>RNA, Neoplasm - metabolism</topic><topic>Transfection</topic><topic>Tumor Cells, Cultured</topic><topic>Tumors</topic><topic>Tumors of the respiratory system and mediastinum</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhu, Y M</creatorcontrib><creatorcontrib>Webster, S J</creatorcontrib><creatorcontrib>Flower, D</creatorcontrib><creatorcontrib>Woll, P J</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Nursing & Allied Health Database</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>British Nursing Database</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>British journal of cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhu, Y M</au><au>Webster, S J</au><au>Flower, D</au><au>Woll, P J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Interleukin-8/CXCL8 is a growth factor for human lung cancer cells</atitle><jtitle>British journal of cancer</jtitle><stitle>Br J Cancer</stitle><addtitle>Br J Cancer</addtitle><date>2004-11-29</date><risdate>2004</risdate><volume>91</volume><issue>11</issue><spage>1970</spage><epage>1976</epage><pages>1970-1976</pages><issn>0007-0920</issn><eissn>1532-1827</eissn><coden>BJCAAI</coden><abstract>Interleukin-8/CXCL8 (IL-8) is a chemokine and angiogenic factor. Recently, IL-8 was identified as an autocrine growth factor in several human cancers. Here, we investigated the expression and function of IL-8 in lung cancer cells. The expressions of IL-8 and its receptors, CXCR1 and CXCR2, were examined in a panel of non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) cell lines. Using reverse transcription–polymerase chain reaction (RT–PCR) and enzyme-linked immunosorbent assay, we found that all NSCLC cell lines tested produced modest or high levels of IL-8 (up to 51 ng ml
−1
10
6
cells
−1
). Expression of CXCR1 and CXCR2 was found by RT–PCR and flow cytometry in two out of three cell lines. In contrast, SCLC cell lines produced very low or undetectable levels of IL-8, but expressed CXCR1 and CXCR2. We next investigated whether IL-8 could act as an autocrine growth factor in two NSCLC cell lines (H460 and MOR/P) expressing both IL-8 and its receptors. We found that cell proliferation was attenuated by anti-IL-8 neutralising antibody to 71 and 76% in H460 and MOR/P, respectively (
P
<0.05). Exogenous IL-8 significantly stimulated cell proliferation in four SCLC cell lines tested in a dose-dependent fashion. Cell proliferation was increased by between 18% (
P
<0.05) and 37% (
P
<0.05). Stimulation of cell proliferation by IL-8 was also demonstrated by analysis of proliferating cell nuclear antigen expression and cell cycle in H69 cells. Furthermore, we investigated which receptor(s) mediated the mitogenic function of IL-8 in lung cancer cells. We found that cell proliferation was significantly reduced by anti-CXCR1 antibody but not by anti-CXCR2 antibody. In conclusion, IL-8 can act as an autocrine and/or paracrine growth factor for lung cancer cells, and the mitogenic function of IL-8 in lung cancer is mediated mainly by CXCR1 receptor.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>15545974</pmid><doi>10.1038/sj.bjc.6602227</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| language | eng |
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| source | MEDLINE; Springer Nature - Complete Springer Journals; Nature Journals Online; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central |
| subjects | Autocrine Communication Biological and medical sciences Biomedical and Life Sciences Biomedicine Cancer Research Carcinoma, Non-Small-Cell Lung - genetics Carcinoma, Non-Small-Cell Lung - metabolism Carcinoma, Small Cell - genetics Carcinoma, Small Cell - metabolism Cell Proliferation Drug Resistance Enzyme-Linked Immunosorbent Assay Epidemiology Experimental Therapeutics Flow Cytometry Humans Interleukin-8 - metabolism Lung cancer Lung Neoplasms - genetics Lung Neoplasms - metabolism Medical sciences Molecular Medicine Oncology Paracrine Communication Pneumology Receptors, Interleukin-8A - genetics Receptors, Interleukin-8A - metabolism Receptors, Interleukin-8B - genetics Receptors, Interleukin-8B - metabolism Recombinant Proteins - isolation & purification Recombinant Proteins - metabolism Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger - genetics RNA, Messenger - metabolism RNA, Neoplasm - genetics RNA, Neoplasm - metabolism Transfection Tumor Cells, Cultured Tumors Tumors of the respiratory system and mediastinum |
| title | Interleukin-8/CXCL8 is a growth factor for human lung cancer cells |
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