STAT3-mediated IGF-2 secretion in the tumour microenvironment elicits innate resistance to anti-IGF-1R antibody
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Lee, Ji-Sun | - |
dc.contributor.author | Kang, Ju-Hee | - |
dc.contributor.author | Boo, Hye-Jin | - |
dc.contributor.author | Hwang, Su-Jung | - |
dc.contributor.author | Hong, Sungyoul | - |
dc.contributor.author | Lee, Su-Chan | - |
dc.contributor.author | Park, Young-Jun | - |
dc.contributor.author | Chung, Tae-Moon | - |
dc.contributor.author | Youn, Hyewon | - |
dc.contributor.author | Lee, Seung Mi | - |
dc.contributor.author | Kim, Byoung Jae | - |
dc.contributor.author | Chung, June-Key | - |
dc.contributor.author | Chung, Yeonseok | - |
dc.contributor.author | William, William N., Jr. | - |
dc.contributor.author | Shin, Young Kee | - |
dc.contributor.author | Lee, Hyo-Jong | - |
dc.contributor.author | Oh, Seung-Hyun | - |
dc.contributor.author | Lee, Ho-Young | - |
dc.date.available | 2020-02-28T07:45:14Z | - |
dc.date.created | 2020-02-06 | - |
dc.date.issued | 2015-10 | - |
dc.identifier.issn | 2041-1723 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/10057 | - |
dc.description.abstract | Drug resistance is a major impediment in medical oncology. Recent studies have emphasized the importance of the tumour microenvironment (TME) to innate resistance, to molecularly targeted therapies. In this study, we investigate the role of TME in resistance to cixutumumab, an anti-IGF-1R monoclonal antibody that has shown limited clinical efficacy. We show that treatment with cixutumumab accelerates tumour infiltration of stromal cells and metastatic tumour growth, and decreases overall survival of mice. Cixutumumab treatment stimulates STAT3-dependent transcriptional upregulation of IGF-2 in cancer cells and recruitment of macrophages and fibroblasts via paracrine IGF-2/IGF-2R activation, resulting in the stroma-derived CXCL8 production, and thus angiogenic and metastatic environment. Silencing IGF-2 or STAT3 expression in cancer cells or IGF-2R or CXCL8 expression in stromal cells significantly inhibits the cancer-stroma communication and vascular endothelial cells' angiogenic activities. These findings suggest that blocking the STAT3/IGF-2/IGF-2R intercellular signalling loop may overcome the adverse consequences of anti-IGF-1R monoclonal antibody-based therapies. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | NATURE PUBLISHING GROUP | - |
dc.relation.isPartOf | NATURE COMMUNICATIONS | - |
dc.subject | GROWTH-FACTOR-II | - |
dc.subject | ENDOTHELIAL-CELLS | - |
dc.subject | DRUG-RESISTANCE | - |
dc.subject | CANCER-CELLS | - |
dc.subject | STEM-CELLS | - |
dc.subject | PHASE-II | - |
dc.subject | RECEPTOR | - |
dc.subject | ANGIOGENESIS | - |
dc.subject | KINASE | - |
dc.subject | FIGITUMUMAB | - |
dc.title | STAT3-mediated IGF-2 secretion in the tumour microenvironment elicits innate resistance to anti-IGF-1R antibody | - |
dc.type | Article | - |
dc.type.rims | ART | - |
dc.description.journalClass | 1 | - |
dc.identifier.wosid | 000364929000001 | - |
dc.identifier.doi | 10.1038/ncomms9499 | - |
dc.identifier.bibliographicCitation | NATURE COMMUNICATIONS, v.6 | - |
dc.identifier.scopusid | 2-s2.0-84944474771 | - |
dc.citation.title | NATURE COMMUNICATIONS | - |
dc.citation.volume | 6 | - |
dc.contributor.affiliatedAuthor | Oh, Seung-Hyun | - |
dc.type.docType | Article | - |
dc.subject.keywordPlus | GROWTH-FACTOR-II | - |
dc.subject.keywordPlus | ENDOTHELIAL-CELLS | - |
dc.subject.keywordPlus | DRUG-RESISTANCE | - |
dc.subject.keywordPlus | CANCER-CELLS | - |
dc.subject.keywordPlus | STEM-CELLS | - |
dc.subject.keywordPlus | PHASE-II | - |
dc.subject.keywordPlus | RECEPTOR | - |
dc.subject.keywordPlus | ANGIOGENESIS | - |
dc.subject.keywordPlus | KINASE | - |
dc.subject.keywordPlus | FIGITUMUMAB | - |
dc.relation.journalResearchArea | Science & Technology - Other Topics | - |
dc.relation.journalWebOfScienceCategory | Multidisciplinary Sciences | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.
1342, Seongnam-daero, Sujeong-gu, Seongnam-si, Gyeonggi-do, Republic of Korea(13120)031-750-5114
COPYRIGHT 2020 Gachon University All Rights Reserved.
Certain data included herein are derived from the © Web of Science of Clarivate Analytics. All rights reserved.
You may not copy or re-distribute this material in whole or in part without the prior written consent of Clarivate Analytics.