Cancer cell-derived IL-8 induces monocytic THP1 cells to secrete IL-8 via the mitogen-activated protein kinase pathway
Aberrant activity of transcription factors in oral squamous cell carcinoma (OSCC) results in the spontaneous secretion of various cytokines and chemokines. Among them, IL-8, owing to its angiogenic activity, promotes the growth of OSCCs. In the present study, we examined the role of IL-8 secreted by...
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| Veröffentlicht in: | Tumor biology 2015-12, Vol.36 (12), p.9171-9177 |
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| creator | Nishio, Yukina Gojoubori, Takahiro Kaneko, Yasuhide Shimizu, Noriyoshi Asano, Masatake |
| description | Aberrant activity of transcription factors in oral squamous cell carcinoma (OSCC) results in the spontaneous secretion of various cytokines and chemokines. Among them, IL-8, owing to its angiogenic activity, promotes the growth of OSCCs. In the present study, we examined the role of IL-8 secreted by OSCCs, on the angiogenic activity of monocytic THP1 cells. Culture supernatant (Ca-sup) augmented IL-8 secretion by THP1 cells, which was found to be significantly reduced following the removal Ca9-22-derived IL-8 from the Ca-sup. IL-8 induction was regulated at the transcriptional level, because real-time PCR demonstrated the augmented IL-8 messenger RNA (mRNA) expression. We further performed the luciferase assay using the 5′-untranslated region of IL-8 gene. Contradictory to our speculations, luciferase activity was not augmented by Ca-sup stimulation. NF-κB-independent IL-8 induction was further confirmed by pre-treating THP1 cells with NF-κB-specific inhibitors. To elucidate the signaling pathway, THP1 was pre-treated with MEK inhibitors. The results demonstrated that pre-treatment of cells with MEK inhibitor drastically reduced IL-8 levels, suggesting the role of MEK. Moreover, Ca-sup was found to increase ERK1/2 phosphorylation in a time-dependent manner. These results indicated that OSCC-derived IL-8 appears to activate angiogenic activity in monocytes within the tumor microenvironment via the mitogen-activated protein kinase (MAPK) pathway. |
| doi_str_mv | 10.1007/s13277-015-3641-6 |
| format | Article |
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Among them, IL-8, owing to its angiogenic activity, promotes the growth of OSCCs. In the present study, we examined the role of IL-8 secreted by OSCCs, on the angiogenic activity of monocytic THP1 cells. Culture supernatant (Ca-sup) augmented IL-8 secretion by THP1 cells, which was found to be significantly reduced following the removal Ca9-22-derived IL-8 from the Ca-sup. IL-8 induction was regulated at the transcriptional level, because real-time PCR demonstrated the augmented IL-8 messenger RNA (mRNA) expression. We further performed the luciferase assay using the 5′-untranslated region of IL-8 gene. Contradictory to our speculations, luciferase activity was not augmented by Ca-sup stimulation. NF-κB-independent IL-8 induction was further confirmed by pre-treating THP1 cells with NF-κB-specific inhibitors. To elucidate the signaling pathway, THP1 was pre-treated with MEK inhibitors. The results demonstrated that pre-treatment of cells with MEK inhibitor drastically reduced IL-8 levels, suggesting the role of MEK. Moreover, Ca-sup was found to increase ERK1/2 phosphorylation in a time-dependent manner. These results indicated that OSCC-derived IL-8 appears to activate angiogenic activity in monocytes within the tumor microenvironment via the mitogen-activated protein kinase (MAPK) pathway.</description><identifier>ISSN: 1010-4283</identifier><identifier>EISSN: 1423-0380</identifier><identifier>DOI: 10.1007/s13277-015-3641-6</identifier><identifier>PMID: 26088451</identifier><language>eng</language><publisher>Dordrecht: Springer Netherlands</publisher><subject>Biomedical and Life Sciences ; Biomedicine ; Cancer ; Cancer Research ; Carcinoma, Squamous Cell - genetics ; Carcinoma, Squamous Cell - pathology ; Cell Line, Tumor ; Cells ; Enzyme Inhibitors - administration & dosage ; Gene Expression Regulation, Neoplastic - drug effects ; Humans ; Interleukin-8 - biosynthesis ; Interleukin-8 - genetics ; Kinases ; Macrophages - pathology ; Mitogen-Activated Protein Kinases - antagonists & inhibitors ; Mitogen-Activated Protein Kinases - genetics ; Monocytes - pathology ; Mouth Neoplasms - genetics ; Mouth Neoplasms - pathology ; NF-kappa B - genetics ; Proteins ; Research Article ; RNA, Messenger - biosynthesis ; Signal Transduction - drug effects</subject><ispartof>Tumor biology, 2015-12, Vol.36 (12), p.9171-9177</ispartof><rights>International Society of Oncology and BioMarkers (ISOBM) 2015</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c475t-127c0d344897d10c946a37dd91c54518f672aeacf19f639a3e10a2fc726c52083</citedby><cites>FETCH-LOGICAL-c475t-127c0d344897d10c946a37dd91c54518f672aeacf19f639a3e10a2fc726c52083</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s13277-015-3641-6$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s13277-015-3641-6$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26088451$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Nishio, Yukina</creatorcontrib><creatorcontrib>Gojoubori, Takahiro</creatorcontrib><creatorcontrib>Kaneko, Yasuhide</creatorcontrib><creatorcontrib>Shimizu, Noriyoshi</creatorcontrib><creatorcontrib>Asano, Masatake</creatorcontrib><title>Cancer cell-derived IL-8 induces monocytic THP1 cells to secrete IL-8 via the mitogen-activated protein kinase pathway</title><title>Tumor biology</title><addtitle>Tumor Biol</addtitle><addtitle>Tumour Biol</addtitle><description>Aberrant activity of transcription factors in oral squamous cell carcinoma (OSCC) results in the spontaneous secretion of various cytokines and chemokines. Among them, IL-8, owing to its angiogenic activity, promotes the growth of OSCCs. In the present study, we examined the role of IL-8 secreted by OSCCs, on the angiogenic activity of monocytic THP1 cells. Culture supernatant (Ca-sup) augmented IL-8 secretion by THP1 cells, which was found to be significantly reduced following the removal Ca9-22-derived IL-8 from the Ca-sup. IL-8 induction was regulated at the transcriptional level, because real-time PCR demonstrated the augmented IL-8 messenger RNA (mRNA) expression. We further performed the luciferase assay using the 5′-untranslated region of IL-8 gene. Contradictory to our speculations, luciferase activity was not augmented by Ca-sup stimulation. NF-κB-independent IL-8 induction was further confirmed by pre-treating THP1 cells with NF-κB-specific inhibitors. To elucidate the signaling pathway, THP1 was pre-treated with MEK inhibitors. The results demonstrated that pre-treatment of cells with MEK inhibitor drastically reduced IL-8 levels, suggesting the role of MEK. Moreover, Ca-sup was found to increase ERK1/2 phosphorylation in a time-dependent manner. These results indicated that OSCC-derived IL-8 appears to activate angiogenic activity in monocytes within the tumor microenvironment via the mitogen-activated protein kinase (MAPK) pathway.</description><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cancer</subject><subject>Cancer Research</subject><subject>Carcinoma, Squamous Cell - genetics</subject><subject>Carcinoma, Squamous Cell - pathology</subject><subject>Cell Line, Tumor</subject><subject>Cells</subject><subject>Enzyme Inhibitors - administration & dosage</subject><subject>Gene Expression Regulation, Neoplastic - drug effects</subject><subject>Humans</subject><subject>Interleukin-8 - biosynthesis</subject><subject>Interleukin-8 - genetics</subject><subject>Kinases</subject><subject>Macrophages - pathology</subject><subject>Mitogen-Activated Protein Kinases - antagonists & inhibitors</subject><subject>Mitogen-Activated Protein Kinases - genetics</subject><subject>Monocytes - pathology</subject><subject>Mouth Neoplasms - genetics</subject><subject>Mouth Neoplasms - pathology</subject><subject>NF-kappa B - genetics</subject><subject>Proteins</subject><subject>Research Article</subject><subject>RNA, Messenger - biosynthesis</subject><subject>Signal Transduction - drug effects</subject><issn>1010-4283</issn><issn>1423-0380</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqNkc9rFDEUx4Mo9pd_gBcJePESzUsyycxRFrWFBXtozyFm3rSpO5k1yWzZ_95spxURhJ4SyOd98977EPIW-Efg3HzKIIUxjEPDpFbA9AtyDEpIxmXLX9Y7B86UaOUROcn5jlew6_RrciQ0b1vVwDHZrVz0mKjHzYb1mMIOe3qxZi0NsZ89ZjpOcfL7Ejy9Or-EBzDTMtGMPmHBBd4FR8st0jGU6QYjc76EnSs1a5umgiHSnyG6jHTryu2925-RV4PbZHzzeJ6S669frlbnbP3928Xq85p5ZZrCQBjPe6lU25keuO-UdtL0fQe-qe23gzbCofMDdIOWnZMI3InBG6F9I3grT8mHJbe28WvGXOwY8mEEF3GaswWjhdTSNPIZaAN1e0JCRd__g95Nc4p1kAdKGlX3XClYKJ-mnBMOdpvC6NLeArcHf3bxZ6sWe_Bnda1595g8_xix_1PxJKwCYgFyfYo3mP76-r-pvwG_R6NS</recordid><startdate>20151201</startdate><enddate>20151201</enddate><creator>Nishio, Yukina</creator><creator>Gojoubori, Takahiro</creator><creator>Kaneko, Yasuhide</creator><creator>Shimizu, Noriyoshi</creator><creator>Asano, Masatake</creator><general>Springer Netherlands</general><general>Springer Nature B.V</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>3V.</scope><scope>7T5</scope><scope>7TO</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>8G5</scope><scope>ABUWG</scope><scope>AFKRA</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>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M7P</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope></search><sort><creationdate>20151201</creationdate><title>Cancer cell-derived IL-8 induces monocytic THP1 cells to secrete IL-8 via the mitogen-activated protein kinase pathway</title><author>Nishio, Yukina ; Gojoubori, Takahiro ; Kaneko, Yasuhide ; Shimizu, Noriyoshi ; Asano, Masatake</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c475t-127c0d344897d10c946a37dd91c54518f672aeacf19f639a3e10a2fc726c52083</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Cancer</topic><topic>Cancer Research</topic><topic>Carcinoma, Squamous Cell - 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Academic</collection><jtitle>Tumor biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Nishio, Yukina</au><au>Gojoubori, Takahiro</au><au>Kaneko, Yasuhide</au><au>Shimizu, Noriyoshi</au><au>Asano, Masatake</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cancer cell-derived IL-8 induces monocytic THP1 cells to secrete IL-8 via the mitogen-activated protein kinase pathway</atitle><jtitle>Tumor biology</jtitle><stitle>Tumor Biol</stitle><addtitle>Tumour Biol</addtitle><date>2015-12-01</date><risdate>2015</risdate><volume>36</volume><issue>12</issue><spage>9171</spage><epage>9177</epage><pages>9171-9177</pages><issn>1010-4283</issn><eissn>1423-0380</eissn><abstract>Aberrant activity of transcription factors in oral squamous cell carcinoma (OSCC) results in the spontaneous secretion of various cytokines and chemokines. Among them, IL-8, owing to its angiogenic activity, promotes the growth of OSCCs. In the present study, we examined the role of IL-8 secreted by OSCCs, on the angiogenic activity of monocytic THP1 cells. Culture supernatant (Ca-sup) augmented IL-8 secretion by THP1 cells, which was found to be significantly reduced following the removal Ca9-22-derived IL-8 from the Ca-sup. IL-8 induction was regulated at the transcriptional level, because real-time PCR demonstrated the augmented IL-8 messenger RNA (mRNA) expression. We further performed the luciferase assay using the 5′-untranslated region of IL-8 gene. Contradictory to our speculations, luciferase activity was not augmented by Ca-sup stimulation. NF-κB-independent IL-8 induction was further confirmed by pre-treating THP1 cells with NF-κB-specific inhibitors. To elucidate the signaling pathway, THP1 was pre-treated with MEK inhibitors. The results demonstrated that pre-treatment of cells with MEK inhibitor drastically reduced IL-8 levels, suggesting the role of MEK. Moreover, Ca-sup was found to increase ERK1/2 phosphorylation in a time-dependent manner. These results indicated that OSCC-derived IL-8 appears to activate angiogenic activity in monocytes within the tumor microenvironment via the mitogen-activated protein kinase (MAPK) pathway.</abstract><cop>Dordrecht</cop><pub>Springer Netherlands</pub><pmid>26088451</pmid><doi>10.1007/s13277-015-3641-6</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Biomedical and Life Sciences Biomedicine Cancer Cancer Research Carcinoma, Squamous Cell - genetics Carcinoma, Squamous Cell - pathology Cell Line, Tumor Cells Enzyme Inhibitors - administration & dosage Gene Expression Regulation, Neoplastic - drug effects Humans Interleukin-8 - biosynthesis Interleukin-8 - genetics Kinases Macrophages - pathology Mitogen-Activated Protein Kinases - antagonists & inhibitors Mitogen-Activated Protein Kinases - genetics Monocytes - pathology Mouth Neoplasms - genetics Mouth Neoplasms - pathology NF-kappa B - genetics Proteins Research Article RNA, Messenger - biosynthesis Signal Transduction - drug effects |
| title | Cancer cell-derived IL-8 induces monocytic THP1 cells to secrete IL-8 via the mitogen-activated protein kinase pathway |
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