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Article: Id1-induced IGF-II and its autocrine/endocrine promotion of esophageal cancer progression and chemoresistance-implications for IGF-II and IGF-IR-targeted therapy

TitleId1-induced IGF-II and its autocrine/endocrine promotion of esophageal cancer progression and chemoresistance-implications for IGF-II and IGF-IR-targeted therapy
Authors
Issue Date2014
PublisherAmerican Association for Cancer Research. The Journal's web site is located at http://clincancerres.aacrjournals.org/
Citation
Clinical Cancer Research, 2014, v. 20 n. 10, p. 2651-2662 How to Cite?
AbstractPURPOSE: To investigate the autocrine/endocrine role of Id1-induced insulin-like growth factor-II (IGF-II) in esophageal cancer, and evaluate the potential of IGF-II- and IGF-type I receptor (IGF-IR)-targeted therapies. EXPERIMENTAL DESIGN: Antibody array-based screening was used to identify differentially secreted growth factors from Id1-overexpressing esophageal cancer cells. In vitro and in vivo assays were performed to confirm the induction of IGF-II by Id1, and to study the autocrine and endocrine effects of IGF-II in promoting esophageal cancer progression. Human esophageal cancer tissue microarray was analyzed for overexpression of IGF-II and its correlation with that of Id1 and phosphorylated AKT (p-AKT). The efficacy of intratumorally injected IGF-II antibody and intraperitoneally injected cixutumumab (fully human monoclonal IGF-IR antibody) was evaluated using in vivo tumor xenograft and experimental metastasis models. RESULTS: Id1 overexpression induced IGF-II secretion, which promoted cancer cell proliferation, survival, and invasion by activating AKT in an autocrine manner. Overexpression of IGF-II was found in 21 of 35 (60%) esophageal cancer tissues and was associated with upregulation of Id1 and p-AKT. IGF-II secreted by Id1-overexpressing esophageal cancer xenograft could instigate the growth of distant esophageal tumors, as well as promote metastasis of circulating cancer cells. Targeting IGF-II and IGF-IR had significant suppressive effects on tumor growth and metastasis in mice. Cixutumumab treatment enhanced the chemosensitivity of tumor xenografts to fluorouracil and cisplatin. CONCLUSIONS: The Id1-IGF-II-IGF-IR-AKT signaling cascade plays an important role in esophageal cancer progression. Blockade of IGF-II/IGF-IR signaling has therapeutic potential in the management of esophageal cancer.
Persistent Identifierhttp://hdl.handle.net/10722/198002
ISSN
2015 Impact Factor: 8.738
2015 SCImago Journal Rankings: 5.314
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorLi, Ben_US
dc.contributor.authorTsao, GSWen_US
dc.contributor.authorChan, KWen_US
dc.contributor.authorLudwig, DLen_US
dc.contributor.authorNovosyadlyy, Ren_US
dc.contributor.authorLi, YYen_US
dc.contributor.authorHe, QYen_US
dc.contributor.authorCheung, Aen_US
dc.date.accessioned2014-06-25T02:38:59Z-
dc.date.available2014-06-25T02:38:59Z-
dc.date.issued2014en_US
dc.identifier.citationClinical Cancer Research, 2014, v. 20 n. 10, p. 2651-2662en_US
dc.identifier.issn1078-0432-
dc.identifier.urihttp://hdl.handle.net/10722/198002-
dc.description.abstractPURPOSE: To investigate the autocrine/endocrine role of Id1-induced insulin-like growth factor-II (IGF-II) in esophageal cancer, and evaluate the potential of IGF-II- and IGF-type I receptor (IGF-IR)-targeted therapies. EXPERIMENTAL DESIGN: Antibody array-based screening was used to identify differentially secreted growth factors from Id1-overexpressing esophageal cancer cells. In vitro and in vivo assays were performed to confirm the induction of IGF-II by Id1, and to study the autocrine and endocrine effects of IGF-II in promoting esophageal cancer progression. Human esophageal cancer tissue microarray was analyzed for overexpression of IGF-II and its correlation with that of Id1 and phosphorylated AKT (p-AKT). The efficacy of intratumorally injected IGF-II antibody and intraperitoneally injected cixutumumab (fully human monoclonal IGF-IR antibody) was evaluated using in vivo tumor xenograft and experimental metastasis models. RESULTS: Id1 overexpression induced IGF-II secretion, which promoted cancer cell proliferation, survival, and invasion by activating AKT in an autocrine manner. Overexpression of IGF-II was found in 21 of 35 (60%) esophageal cancer tissues and was associated with upregulation of Id1 and p-AKT. IGF-II secreted by Id1-overexpressing esophageal cancer xenograft could instigate the growth of distant esophageal tumors, as well as promote metastasis of circulating cancer cells. Targeting IGF-II and IGF-IR had significant suppressive effects on tumor growth and metastasis in mice. Cixutumumab treatment enhanced the chemosensitivity of tumor xenografts to fluorouracil and cisplatin. CONCLUSIONS: The Id1-IGF-II-IGF-IR-AKT signaling cascade plays an important role in esophageal cancer progression. Blockade of IGF-II/IGF-IR signaling has therapeutic potential in the management of esophageal cancer.-
dc.languageengen_US
dc.publisherAmerican Association for Cancer Research. The Journal's web site is located at http://clincancerres.aacrjournals.org/-
dc.relation.ispartofClinical Cancer Researchen_US
dc.titleId1-induced IGF-II and its autocrine/endocrine promotion of esophageal cancer progression and chemoresistance-implications for IGF-II and IGF-IR-targeted therapyen_US
dc.typeArticleen_US
dc.identifier.emailLi, B: libinhku@hkucc.hku.hken_US
dc.identifier.emailTsao, GSW: gswtsao@hku.hken_US
dc.identifier.emailChan, KW: hrmtckw@hku.hken_US
dc.identifier.emailLi, YY: yyli@hku.hken_US
dc.identifier.emailCheung, A: lmcheung@hku.hken_US
dc.identifier.authorityTsao, GSW=rp00399en_US
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1158/1078-0432.CCR-13-2735en_US
dc.identifier.pmid24599933-
dc.identifier.hkuros229258en_US
dc.identifier.volume20-
dc.identifier.issue10-
dc.identifier.spage2651en_US
dc.identifier.epage2662en_US
dc.identifier.isiWOS:000336720200017-
dc.publisher.placeUnited States-

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