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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
8
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pubmed:dateCreated |
2005-7-22
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pubmed:abstractText |
Most circulating tumor cells die within 24 h of entering the hepatic microvasculature because their arrest initiates an ischemia-reperfusion (I/R) injury that is cytotoxic. Human colorectal carcinomas (CRC) produce the glycoprotein Carcinoembryonic Antigen (CEA) that increases experimental liver metastasis in nude mice. Since CEA induces release of IL-6 and IL-10, we hypothesized that CEA inhibits the I/R injury through a Kupffer cell-mediated cytokine-dependent pathway. We assessed cytokine effects in CRC co-cultured with liver and in vivo. Human CRC prelabeled with fluorescent dyes were incubated with a reoxygenated suspension of ischemic nude mouse liver fragments in a bioreactor. CEA, rhIL-6 or rhIL-10 were either administered to the donor mice prior to hepatic ischemia or during co-culture. Liver donors were athymic nude or iNOS, IL-6 or IL-10 knock out mice. Ischemic-reoxygenated liver kills Clone A CRC through production of nitric oxide (NO) and superoxide anion. Treatment of liver donors with CEA prior to hepatic ischemia inhibited this in vitro cytotoxicity through an IL-10 and Kupffer cell dependent pathway that inhibited NF-kappaB activation, NO production and iNOS upregulation. IL-10 but not IL-6 enhanced CRC survival in nude mouse liver in vivo. Thus, CEA enhanced metastasis by inducing IL-10 to inhibit iNOS upregulation in host liver.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Carcinoembryonic Antigen,
http://linkedlifedata.com/resource/pubmed/chemical/Fluorescent Dyes,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-10,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-6,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/NOS2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide Synthase,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide Synthase Type II,
http://linkedlifedata.com/resource/pubmed/chemical/Nos2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Oxygen,
http://linkedlifedata.com/resource/pubmed/chemical/Superoxides
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pubmed:status |
MEDLINE
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pubmed:issn |
0262-0898
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
21
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
709-17
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pubmed:dateRevised |
2011-10-27
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pubmed:meshHeading |
pubmed-meshheading:16035616-Animals,
pubmed-meshheading:16035616-Carcinoembryonic Antigen,
pubmed-meshheading:16035616-Cell Survival,
pubmed-meshheading:16035616-Coculture Techniques,
pubmed-meshheading:16035616-Colorectal Neoplasms,
pubmed-meshheading:16035616-Fluorescent Dyes,
pubmed-meshheading:16035616-Humans,
pubmed-meshheading:16035616-Interleukin-10,
pubmed-meshheading:16035616-Interleukin-6,
pubmed-meshheading:16035616-Kupffer Cells,
pubmed-meshheading:16035616-Liver,
pubmed-meshheading:16035616-Liver Neoplasms,
pubmed-meshheading:16035616-Male,
pubmed-meshheading:16035616-Mice,
pubmed-meshheading:16035616-Mice, Inbred C57BL,
pubmed-meshheading:16035616-Mice, Knockout,
pubmed-meshheading:16035616-Mice, Nude,
pubmed-meshheading:16035616-NF-kappa B,
pubmed-meshheading:16035616-Nitric Oxide,
pubmed-meshheading:16035616-Nitric Oxide Synthase,
pubmed-meshheading:16035616-Nitric Oxide Synthase Type II,
pubmed-meshheading:16035616-Oxidative Stress,
pubmed-meshheading:16035616-Oxygen,
pubmed-meshheading:16035616-Reperfusion Injury,
pubmed-meshheading:16035616-Signal Transduction,
pubmed-meshheading:16035616-Superoxides
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pubmed:year |
2004
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pubmed:articleTitle |
Carcinoembryonic antigen promotes tumor cell survival in liver through an IL-10-dependent pathway.
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pubmed:affiliation |
Department of Oncology, Georgetown University Medical Center, Washington, DC, USA. jmj25@georgetown.edu
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, N.I.H., Extramural
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