Interleukin‐8 is associated with proliferation, migration, angiogenesis and chemosensitivity in vitro and in vivo in colon cancer cell line models
Interleukin‐8 (IL‐8), a chemokine with a defining CXC amino acid motif, is known to possess tumorigenic and proangiogenic properties. Overexpression of IL‐8 has been detected in many human tumors, including colorectal cancer (CRC), and is associated with poor prognosis. The goal of our study was to...
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| Veröffentlicht in: | International journal of cancer 2011-05, Vol.128 (9), p.2038-2049 |
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| creator | Ning, Yan Manegold, Philipp C. Hong, Young Kwon Zhang, Wu Pohl, Alexandra Lurje, Georg Winder, Thomas Yang, Dongyun LaBonte, Melissa J. Wilson, Peter M. Ladner, Robert D. Lenz, Heinz‐Josef |
| description | Interleukin‐8 (IL‐8), a chemokine with a defining CXC amino acid motif, is known to possess tumorigenic and proangiogenic properties. Overexpression of IL‐8 has been detected in many human tumors, including colorectal cancer (CRC), and is associated with poor prognosis. The goal of our study was to determine the role of IL‐8 overexpression in CRC cells in vitro and in vivo. We stably transfected the IL‐8 cDNA into two human colon cancer cell lines, HCT116 and Caco2, and selected IL‐8‐secreting transfectants. Real‐time RT‐PCR confirmed that IL‐8 mRNA was overexpressed in IL‐8 transfectants with 45‐ to 85‐fold higher than parental cells. The IL‐8‐transfected clones secreted 19‐ to 28‐fold more IL‐8 protein than control and parental cells as detected by ELISA. The IL‐8 transfectants demonstrated increased cellular proliferation, cell migration and invasion based on functional assays. Growth inhibition studies showed that IL‐8 overexpression lead to a significant resistance to oxaliplatin (p < 0.0001). Inhibition of IL‐8 overexpression with small interfering RNA reversed the observed increases in tumorigenic functions and oxaliplatin resistance, suggesting that IL‐8 not only provides a proliferative advantage but also promotes the metastatic potential of colon cancer cells. Using a tumor xenograft model, IL‐8‐expressing cells formed significantly larger tumors than the control cells with increased microvessel density. Together, these findings indicate that overexpression of IL‐8 promotes tumor growth, metastasis, chemoresistance and angiogenesis, implying IL‐8 to be an important therapeutic target in CRC. |
| doi_str_mv | 10.1002/ijc.25562 |
| format | Article |
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Overexpression of IL‐8 has been detected in many human tumors, including colorectal cancer (CRC), and is associated with poor prognosis. The goal of our study was to determine the role of IL‐8 overexpression in CRC cells in vitro and in vivo. We stably transfected the IL‐8 cDNA into two human colon cancer cell lines, HCT116 and Caco2, and selected IL‐8‐secreting transfectants. Real‐time RT‐PCR confirmed that IL‐8 mRNA was overexpressed in IL‐8 transfectants with 45‐ to 85‐fold higher than parental cells. The IL‐8‐transfected clones secreted 19‐ to 28‐fold more IL‐8 protein than control and parental cells as detected by ELISA. The IL‐8 transfectants demonstrated increased cellular proliferation, cell migration and invasion based on functional assays. Growth inhibition studies showed that IL‐8 overexpression lead to a significant resistance to oxaliplatin (p < 0.0001). Inhibition of IL‐8 overexpression with small interfering RNA reversed the observed increases in tumorigenic functions and oxaliplatin resistance, suggesting that IL‐8 not only provides a proliferative advantage but also promotes the metastatic potential of colon cancer cells. Using a tumor xenograft model, IL‐8‐expressing cells formed significantly larger tumors than the control cells with increased microvessel density. Together, these findings indicate that overexpression of IL‐8 promotes tumor growth, metastasis, chemoresistance and angiogenesis, implying IL‐8 to be an important therapeutic target in CRC.</description><identifier>ISSN: 0020-7136</identifier><identifier>ISSN: 1097-0215</identifier><identifier>EISSN: 1097-0215</identifier><identifier>DOI: 10.1002/ijc.25562</identifier><identifier>PMID: 20648559</identifier><identifier>CODEN: IJCNAW</identifier><language>eng</language><publisher>Hoboken: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>Amino acids ; Angiogenesis ; Animals ; Biological and medical sciences ; Blotting, Western ; Caco-2 Cells ; Cell culture ; Cell migration ; Cell Movement ; Cell Proliferation ; Chemokines ; Chemoresistance ; Colon cancer ; Colonic Neoplasms - blood supply ; Colonic Neoplasms - metabolism ; Colonic Neoplasms - pathology ; Colorectal cancer ; Drug Resistance, Neoplasm - physiology ; Enzyme-Linked Immunosorbent Assay ; Gastroenterology. Liver. Pancreas. Abdomen ; HCT116 Cells ; Humans ; Immunohistochemistry ; Interleukin 8 ; Interleukin-8 - metabolism ; Medical sciences ; Metastases ; Mice ; mRNA ; Neovascularization, Pathologic - metabolism ; oxaliplatin ; Polymerase chain reaction ; Prognosis ; proliferation ; Reverse Transcriptase Polymerase Chain Reaction ; siRNA ; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus ; Transfection ; Tumor cell lines ; Tumors ; Xenograft Model Antitumor Assays ; Xenografts</subject><ispartof>International journal of cancer, 2011-05, Vol.128 (9), p.2038-2049</ispartof><rights>Copyright © 2010 UICC</rights><rights>2015 INIST-CNRS</rights><rights>Copyright © 2010 UICC.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4772-872930649526c78a4182286aed243e6bf76551af1d4326064af148a7c363cf3f3</citedby><cites>FETCH-LOGICAL-c4772-872930649526c78a4182286aed243e6bf76551af1d4326064af148a7c363cf3f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fijc.25562$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fijc.25562$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,314,776,780,881,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=23969157$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20648559$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ning, Yan</creatorcontrib><creatorcontrib>Manegold, Philipp C.</creatorcontrib><creatorcontrib>Hong, Young Kwon</creatorcontrib><creatorcontrib>Zhang, Wu</creatorcontrib><creatorcontrib>Pohl, Alexandra</creatorcontrib><creatorcontrib>Lurje, Georg</creatorcontrib><creatorcontrib>Winder, Thomas</creatorcontrib><creatorcontrib>Yang, Dongyun</creatorcontrib><creatorcontrib>LaBonte, Melissa J.</creatorcontrib><creatorcontrib>Wilson, Peter M.</creatorcontrib><creatorcontrib>Ladner, Robert D.</creatorcontrib><creatorcontrib>Lenz, Heinz‐Josef</creatorcontrib><title>Interleukin‐8 is associated with proliferation, migration, angiogenesis and chemosensitivity in vitro and in vivo in colon cancer cell line models</title><title>International journal of cancer</title><addtitle>Int J Cancer</addtitle><description>Interleukin‐8 (IL‐8), a chemokine with a defining CXC amino acid motif, is known to possess tumorigenic and proangiogenic properties. Overexpression of IL‐8 has been detected in many human tumors, including colorectal cancer (CRC), and is associated with poor prognosis. The goal of our study was to determine the role of IL‐8 overexpression in CRC cells in vitro and in vivo. We stably transfected the IL‐8 cDNA into two human colon cancer cell lines, HCT116 and Caco2, and selected IL‐8‐secreting transfectants. Real‐time RT‐PCR confirmed that IL‐8 mRNA was overexpressed in IL‐8 transfectants with 45‐ to 85‐fold higher than parental cells. The IL‐8‐transfected clones secreted 19‐ to 28‐fold more IL‐8 protein than control and parental cells as detected by ELISA. The IL‐8 transfectants demonstrated increased cellular proliferation, cell migration and invasion based on functional assays. Growth inhibition studies showed that IL‐8 overexpression lead to a significant resistance to oxaliplatin (p < 0.0001). Inhibition of IL‐8 overexpression with small interfering RNA reversed the observed increases in tumorigenic functions and oxaliplatin resistance, suggesting that IL‐8 not only provides a proliferative advantage but also promotes the metastatic potential of colon cancer cells. Using a tumor xenograft model, IL‐8‐expressing cells formed significantly larger tumors than the control cells with increased microvessel density. Together, these findings indicate that overexpression of IL‐8 promotes tumor growth, metastasis, chemoresistance and angiogenesis, implying IL‐8 to be an important therapeutic target in CRC.</description><subject>Amino acids</subject><subject>Angiogenesis</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Blotting, Western</subject><subject>Caco-2 Cells</subject><subject>Cell culture</subject><subject>Cell migration</subject><subject>Cell Movement</subject><subject>Cell Proliferation</subject><subject>Chemokines</subject><subject>Chemoresistance</subject><subject>Colon cancer</subject><subject>Colonic Neoplasms - blood supply</subject><subject>Colonic Neoplasms - metabolism</subject><subject>Colonic Neoplasms - pathology</subject><subject>Colorectal cancer</subject><subject>Drug Resistance, Neoplasm - physiology</subject><subject>Enzyme-Linked Immunosorbent Assay</subject><subject>Gastroenterology. Liver. Pancreas. Abdomen</subject><subject>HCT116 Cells</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Interleukin 8</subject><subject>Interleukin-8 - metabolism</subject><subject>Medical sciences</subject><subject>Metastases</subject><subject>Mice</subject><subject>mRNA</subject><subject>Neovascularization, Pathologic - metabolism</subject><subject>oxaliplatin</subject><subject>Polymerase chain reaction</subject><subject>Prognosis</subject><subject>proliferation</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>siRNA</subject><subject>Stomach. Duodenum. Small intestine. Colon. Rectum. Anus</subject><subject>Transfection</subject><subject>Tumor cell lines</subject><subject>Tumors</subject><subject>Xenograft Model Antitumor Assays</subject><subject>Xenografts</subject><issn>0020-7136</issn><issn>1097-0215</issn><issn>1097-0215</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kUuOEzEQhlsIxISBBRdA3iBAomf8aD96g4QiHkEjsYG15XFXJx7cdrA7GWXHEVhwQk6CO8kMsICNq0r1-S-X_6p6TPAZwZieuyt7RjkX9E41I7iVNaaE361mpYdrSZg4qR7kfIUxIRw396sTikWjOG9n1Y9FGCF52Hxx4ee37wq5jEzO0TozQoeu3bhC6xS96yGZ0cXwEg1ueZOasHRxCQHydC10yK5giBlCdqPbunGHXEAlprjv7ottnKKNPpbTBAsJWfAeeRcADbEDnx9W93rjMzw6xtPq89s3n-bv64uP7xbz1xe1baSktZK0ZWWTllNhpTINUZQqYaCjDQNx2UvBOTE96RpGRQFL2igjLRPM9qxnp9Wrg-56czlAZyGMyXi9Tm4waaejcfrvTnArvYxbzTBrJeFF4NlRIMWvG8ijHlyetjEB4iZrxUWDheK0kM__S5JileJMqAl9cUBtijkn6G8fRLCe_NbFb733u7BP_tzglrwxuABPj4DJ1vg-lR93-TfHWtESLgt3fuCunYfdvyfqxYf5YfQvqxvE6g</recordid><startdate>20110501</startdate><enddate>20110501</enddate><creator>Ning, Yan</creator><creator>Manegold, Philipp C.</creator><creator>Hong, Young Kwon</creator><creator>Zhang, Wu</creator><creator>Pohl, Alexandra</creator><creator>Lurje, Georg</creator><creator>Winder, Thomas</creator><creator>Yang, Dongyun</creator><creator>LaBonte, Melissa J.</creator><creator>Wilson, Peter M.</creator><creator>Ladner, Robert D.</creator><creator>Lenz, Heinz‐Josef</creator><general>Wiley Subscription Services, Inc., A Wiley Company</general><general>Wiley-Blackwell</general><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>7T5</scope><scope>H94</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20110501</creationdate><title>Interleukin‐8 is associated with proliferation, migration, angiogenesis and chemosensitivity in vitro and in vivo in colon cancer cell line models</title><author>Ning, Yan ; Manegold, Philipp C. ; Hong, Young Kwon ; Zhang, Wu ; Pohl, Alexandra ; Lurje, Georg ; Winder, Thomas ; Yang, Dongyun ; LaBonte, Melissa J. ; Wilson, Peter M. ; Ladner, Robert D. ; Lenz, Heinz‐Josef</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4772-872930649526c78a4182286aed243e6bf76551af1d4326064af148a7c363cf3f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Amino acids</topic><topic>Angiogenesis</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Blotting, Western</topic><topic>Caco-2 Cells</topic><topic>Cell culture</topic><topic>Cell migration</topic><topic>Cell Movement</topic><topic>Cell Proliferation</topic><topic>Chemokines</topic><topic>Chemoresistance</topic><topic>Colon cancer</topic><topic>Colonic Neoplasms - blood supply</topic><topic>Colonic Neoplasms - metabolism</topic><topic>Colonic Neoplasms - pathology</topic><topic>Colorectal cancer</topic><topic>Drug Resistance, Neoplasm - physiology</topic><topic>Enzyme-Linked Immunosorbent Assay</topic><topic>Gastroenterology. Liver. Pancreas. Abdomen</topic><topic>HCT116 Cells</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Interleukin 8</topic><topic>Interleukin-8 - metabolism</topic><topic>Medical sciences</topic><topic>Metastases</topic><topic>Mice</topic><topic>mRNA</topic><topic>Neovascularization, Pathologic - metabolism</topic><topic>oxaliplatin</topic><topic>Polymerase chain reaction</topic><topic>Prognosis</topic><topic>proliferation</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>siRNA</topic><topic>Stomach. Duodenum. Small intestine. Colon. Rectum. Anus</topic><topic>Transfection</topic><topic>Tumor cell lines</topic><topic>Tumors</topic><topic>Xenograft Model Antitumor Assays</topic><topic>Xenografts</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ning, Yan</creatorcontrib><creatorcontrib>Manegold, Philipp C.</creatorcontrib><creatorcontrib>Hong, Young Kwon</creatorcontrib><creatorcontrib>Zhang, Wu</creatorcontrib><creatorcontrib>Pohl, Alexandra</creatorcontrib><creatorcontrib>Lurje, Georg</creatorcontrib><creatorcontrib>Winder, Thomas</creatorcontrib><creatorcontrib>Yang, Dongyun</creatorcontrib><creatorcontrib>LaBonte, Melissa J.</creatorcontrib><creatorcontrib>Wilson, Peter M.</creatorcontrib><creatorcontrib>Ladner, Robert D.</creatorcontrib><creatorcontrib>Lenz, Heinz‐Josef</creatorcontrib><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>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>International journal of cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ning, Yan</au><au>Manegold, Philipp C.</au><au>Hong, Young Kwon</au><au>Zhang, Wu</au><au>Pohl, Alexandra</au><au>Lurje, Georg</au><au>Winder, Thomas</au><au>Yang, Dongyun</au><au>LaBonte, Melissa J.</au><au>Wilson, Peter M.</au><au>Ladner, Robert D.</au><au>Lenz, Heinz‐Josef</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Interleukin‐8 is associated with proliferation, migration, angiogenesis and chemosensitivity in vitro and in vivo in colon cancer cell line models</atitle><jtitle>International journal of cancer</jtitle><addtitle>Int J Cancer</addtitle><date>2011-05-01</date><risdate>2011</risdate><volume>128</volume><issue>9</issue><spage>2038</spage><epage>2049</epage><pages>2038-2049</pages><issn>0020-7136</issn><issn>1097-0215</issn><eissn>1097-0215</eissn><coden>IJCNAW</coden><abstract>Interleukin‐8 (IL‐8), a chemokine with a defining CXC amino acid motif, is known to possess tumorigenic and proangiogenic properties. Overexpression of IL‐8 has been detected in many human tumors, including colorectal cancer (CRC), and is associated with poor prognosis. The goal of our study was to determine the role of IL‐8 overexpression in CRC cells in vitro and in vivo. We stably transfected the IL‐8 cDNA into two human colon cancer cell lines, HCT116 and Caco2, and selected IL‐8‐secreting transfectants. Real‐time RT‐PCR confirmed that IL‐8 mRNA was overexpressed in IL‐8 transfectants with 45‐ to 85‐fold higher than parental cells. The IL‐8‐transfected clones secreted 19‐ to 28‐fold more IL‐8 protein than control and parental cells as detected by ELISA. The IL‐8 transfectants demonstrated increased cellular proliferation, cell migration and invasion based on functional assays. Growth inhibition studies showed that IL‐8 overexpression lead to a significant resistance to oxaliplatin (p < 0.0001). Inhibition of IL‐8 overexpression with small interfering RNA reversed the observed increases in tumorigenic functions and oxaliplatin resistance, suggesting that IL‐8 not only provides a proliferative advantage but also promotes the metastatic potential of colon cancer cells. Using a tumor xenograft model, IL‐8‐expressing cells formed significantly larger tumors than the control cells with increased microvessel density. Together, these findings indicate that overexpression of IL‐8 promotes tumor growth, metastasis, chemoresistance and angiogenesis, implying IL‐8 to be an important therapeutic target in CRC.</abstract><cop>Hoboken</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>20648559</pmid><doi>10.1002/ijc.25562</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Amino acids Angiogenesis Animals Biological and medical sciences Blotting, Western Caco-2 Cells Cell culture Cell migration Cell Movement Cell Proliferation Chemokines Chemoresistance Colon cancer Colonic Neoplasms - blood supply Colonic Neoplasms - metabolism Colonic Neoplasms - pathology Colorectal cancer Drug Resistance, Neoplasm - physiology Enzyme-Linked Immunosorbent Assay Gastroenterology. Liver. Pancreas. Abdomen HCT116 Cells Humans Immunohistochemistry Interleukin 8 Interleukin-8 - metabolism Medical sciences Metastases Mice mRNA Neovascularization, Pathologic - metabolism oxaliplatin Polymerase chain reaction Prognosis proliferation Reverse Transcriptase Polymerase Chain Reaction siRNA Stomach. Duodenum. Small intestine. Colon. Rectum. Anus Transfection Tumor cell lines Tumors Xenograft Model Antitumor Assays Xenografts |
| title | Interleukin‐8 is associated with proliferation, migration, angiogenesis and chemosensitivity in vitro and in vivo in colon cancer cell line models |
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