https://scholars.lib.ntu.edu.tw/handle/123456789/458234
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.author | Lo C.-W | en_US |
dc.contributor.author | Chen M.-W | en_US |
dc.contributor.author | Hsiao M | en_US |
dc.contributor.author | Wang S | en_US |
dc.contributor.author | CHI-AN CHEN | en_US |
dc.contributor.author | Hsiao S.-M | en_US |
dc.contributor.author | Chang J.-S | en_US |
dc.contributor.author | Lai T.-C | en_US |
dc.contributor.author | Rose-John S | en_US |
dc.contributor.author | Kuo M.-L | en_US |
dc.contributor.author | LING-HUNG WEI | en_US |
dc.creator | LING-HUNG WEI;Kuo M.-L;Rose-John S;Lai T.-C;Chang J.-S;Hsiao S.-M;Chen C.-A;Wang S;Hsiao M;Chen M.-W;Lo C.-W | - |
dc.date.accessioned | 2020-02-12T05:48:28Z | - |
dc.date.available | 2020-02-12T05:48:28Z | - |
dc.date.issued | 2011 | - |
dc.identifier.issn | 0008-5472 | - |
dc.identifier.uri | https://scholars.lib.ntu.edu.tw/handle/123456789/458234 | - |
dc.description.abstract | Classic signaling by the proinflammatory cytokine interleukin 6 (IL-6) involves its binding to target cells that express the membrane-bound IL-6 receptor a. However, an alternate signaling pathway exists in which soluble IL-6 receptor (sIL-6Rα) can bind IL-6 and activate target cells that lack mIL-6Rα, such as endothelial cells. This alternate pathway, also termed trans-signaling, serves as the major IL-6 signaling pathway in various pathologic proinflammatory conditions including cancer. Here we report that sIL-6Rα is elevated in malignant ascites from ovarian cancer patients, where it is associated with poor prognosis. IL-6 trans-signaling on endothelial cells prevented chemotherapy-induced apoptosis, induced endothelial hyperpermeability, and increased transendothelial migration of ovarian cancer cells. Selective blockade of the MAPK pathway with ERK inhibitor PD98059 reduced IL-6/sIL-6Rα-mediated endothelial hyperpermeability. ERK activation by the IL-6/sIL-6Rα complex increased endothelial integrity via Src kinase activation and Y685 phosphorylation of VE-cadherin. Selective targeting of IL-6 trans-signaling in vivo reduced ascites formation and enhanced the taxane sensitivity of intraperitoneal human ovarian tumor xenografts in mice. Collectively, our results show that increased levels of sIL-6Rα found in ovarian cancer ascites drive IL-6 trans-signaling on endothelial cells, thereby contributing to cancer progression. Selective blockade of IL-6 trans-signaling may offer a promising therapeutic strategy to improve the management of patients with advanced ovarian cancer. ? 2010 American Association for Cancer Research. | - |
dc.relation.ispartof | Cancer Research | - |
dc.subject.classification | [SDGs]SDG3 | - |
dc.subject.other | 2 (2 amino 3 methoxyphenyl)chromone; cadherin; interleukin 6 receptor alpha; mitogen activated protein kinase; protein tyrosine kinase; taxane derivative; animal cell; animal experiment; animal model; animal tissue; apoptosis; article; ascites; cancer cell; cancer chemotherapy; cancer growth; cancer patient; cell membrane permeability; cell migration; controlled study; drug sensitivity; endothelium cell; female; human; human cell; human tissue; in vivo study; mouse; nonhuman; ovary cancer; priority journal; prognosis; protein blood level; sensitivity analysis; signal transduction; tumor xenograft; Animals; Antigens, CD; Ascites; Cadherins; Cell Adhesion; Cell Line, Tumor; Drug Synergism; Endothelial Cells; Female; Humans; Interleukin-6; MAP Kinase Signaling System; Mice; Mice, Inbred NOD; Mice, SCID; Mitogen-Activated Protein Kinases; Neovascularization, Pathologic; Ovarian Neoplasms; Paclitaxel; Phosphorylation; Receptors, Interleukin-6; Recombinant Fusion Proteins; Signal Transduction; src-Family Kinases; Xenograft Model Antitumor Assays | - |
dc.title | IL-6 trans-signaling in formation and progression of malignant ascites in ovarian cancer | en_US |
dc.type | journal article | en |
dc.identifier.doi | 10.1158/0008-5472.CAN-10-1496 | - |
dc.identifier.pmid | 21123455 | - |
dc.identifier.scopus | 2-s2.0-78751549236 | - |
dc.relation.pages | 424-434 | - |
dc.relation.journalvolume | 71 | - |
dc.relation.journalissue | 2 | - |
item.cerifentitytype | Publications | - |
item.fulltext | no fulltext | - |
item.openairecristype | http://purl.org/coar/resource_type/c_6501 | - |
item.openairetype | journal article | - |
item.grantfulltext | none | - |
crisitem.author.dept | Obstetrics & Gynecology-NTUH | - |
crisitem.author.dept | Obstetrics & Gynecology | - |
crisitem.author.dept | Obstetrics & Gynecology | - |
crisitem.author.dept | Obstetrics & Gynecology-NTUH | - |
crisitem.author.dept | Oncology-NTUH | - |
crisitem.author.orcid | 0000-0001-6670-7939 | - |
crisitem.author.orcid | 0000-0001-8789-0859 | - |
crisitem.author.parentorg | National Taiwan University Hospital | - |
crisitem.author.parentorg | College of Medicine | - |
crisitem.author.parentorg | College of Medicine | - |
crisitem.author.parentorg | National Taiwan University Hospital | - |
crisitem.author.parentorg | National Taiwan University Hospital | - |
顯示於: | 醫學系 |
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