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Conference Paper: Role of Id1-IGF2-VEGF-VEGFR relay in esophageal tumorigenesis

TitleRole of Id1-IGF2-VEGF-VEGFR relay in esophageal tumorigenesis
Authors
KeywordsMedical sciences
Oncology
Issue Date2014
PublisherPergamon. The Journal's web site is located at http://www.elsevier.com/locate/ejca
Citation
The 23rd Biennial Congress of the European Association for Cancer Research (EACR-23), Munich, Germany, 5-8 July 2014. In European Journal of Cancer, 2014, v. 50 suppl. 5, p. S35-S36, abstract no. 161 How to Cite?
AbstractINTRODUCTION: It is increasingly evident that the close interactions between cancer cells and other cells in the tumor microenvironment help drive tumor progression. Esophageal squamous cell carcinoma (ESCC) is a highly lethal disease, and there is an association between poor clinical outcome and Id1 overexpression in ESCC. We previously reported that Id1 induces the expression and secretion of insulin-like growth factor-2 (IGF2) which promotes esophageal cancer progression and metastasis in an autocrine manner. In this study, we aim to investigate the paracrine effect of Id1-induced IGF2 on esophageal fibroblasts, and the stimulatory effects and roles of fibroblast-secreted vascular endothelial growth factor (VEGF) on endothelial cells and VEGF receptor (VEGFR)-positive bone marrow cells during esophageal tumorigenesis. MATERIALS AND METHODS: Human ESCC cell lines with ectopic expression of Id1, co-expression of Id1 and shRNA against IGF2 (shIGF2), or empty vector were established. Bone marrow was harvested from femurs and tibias of nude mice for isolation of VEGFR1+ bone marrow cells by flow cytometry. Cell proliferation and migration were determined using MTT and chamber migration assays respectively. Western blot and ELISA were used to determine the protein expression and concentration in cell lysates and conditioned medium (CM). Tube formation assay was used to analyze the in vitro angiogenic ability of endothelial cells. Human ESCC cells were subcutaneously injected into the flanks of nude mice to establish the tumor xenografts. RESULTS AND DISCUSSION: Our data from Western blot and ELISA showed that the addition of CM from the ESCC cells with overexpression of Id1 or recombinant human IGF2 alone could promote esophageal fibroblasts to produce VEGF in vitro, and co-expression of shIGF2 or neutralizing antibody against IGF2 greatly diminished this effect. We also found that the CM collected from IGF2-activated fibroblasts could enhance the proliferation, tube-formation and migration abilities of human umbilical vein endothelial cells (HUVECs). The addition of VEGF-neutralizing antibody effectively attenuated these stimulatory effects. In addition, our results showed that the CM collected from IGF2-activated fibroblasts increased the mobility of VEGFR1+ bone marrow cells. Furthermore, data from in vivo experiment showed that bone marrow cells harvested from nude mice bearing Id1-expressing tumor xenografts had tumor-promoting activity when co-injected subcutaneously with untransfected ESCC cells into new groups of nude mice. CONCLUSIONS: Id1-overexpressing ESCC cells secrete IGF2 and educate stromal fibroblasts to secrete VEGF, which may in turn activate and mobilize endothelial cells as well as bone marrow-derived hematopoietic-progenitor cells to promote tumor angiogenesis.
DescriptionThis journal suppl. entitled: 23rd Biennial Congress of the European Association for Cancer Research ... 2014
Poster Session
Persistent Identifierhttp://hdl.handle.net/10722/201152
ISSN
2015 Impact Factor: 6.163
2015 SCImago Journal Rankings: 3.152

 

DC FieldValueLanguage
dc.contributor.authorCheung, ALMen_US
dc.contributor.authorXu, Wen_US
dc.contributor.authorLi, Ben_US
dc.contributor.authorTsao, SWen_US
dc.contributor.authorChan, KWen_US
dc.date.accessioned2014-08-21T07:15:34Z-
dc.date.available2014-08-21T07:15:34Z-
dc.date.issued2014en_US
dc.identifier.citationThe 23rd Biennial Congress of the European Association for Cancer Research (EACR-23), Munich, Germany, 5-8 July 2014. In European Journal of Cancer, 2014, v. 50 suppl. 5, p. S35-S36, abstract no. 161en_US
dc.identifier.issn0959-8049-
dc.identifier.urihttp://hdl.handle.net/10722/201152-
dc.descriptionThis journal suppl. entitled: 23rd Biennial Congress of the European Association for Cancer Research ... 2014-
dc.descriptionPoster Session-
dc.description.abstractINTRODUCTION: It is increasingly evident that the close interactions between cancer cells and other cells in the tumor microenvironment help drive tumor progression. Esophageal squamous cell carcinoma (ESCC) is a highly lethal disease, and there is an association between poor clinical outcome and Id1 overexpression in ESCC. We previously reported that Id1 induces the expression and secretion of insulin-like growth factor-2 (IGF2) which promotes esophageal cancer progression and metastasis in an autocrine manner. In this study, we aim to investigate the paracrine effect of Id1-induced IGF2 on esophageal fibroblasts, and the stimulatory effects and roles of fibroblast-secreted vascular endothelial growth factor (VEGF) on endothelial cells and VEGF receptor (VEGFR)-positive bone marrow cells during esophageal tumorigenesis. MATERIALS AND METHODS: Human ESCC cell lines with ectopic expression of Id1, co-expression of Id1 and shRNA against IGF2 (shIGF2), or empty vector were established. Bone marrow was harvested from femurs and tibias of nude mice for isolation of VEGFR1+ bone marrow cells by flow cytometry. Cell proliferation and migration were determined using MTT and chamber migration assays respectively. Western blot and ELISA were used to determine the protein expression and concentration in cell lysates and conditioned medium (CM). Tube formation assay was used to analyze the in vitro angiogenic ability of endothelial cells. Human ESCC cells were subcutaneously injected into the flanks of nude mice to establish the tumor xenografts. RESULTS AND DISCUSSION: Our data from Western blot and ELISA showed that the addition of CM from the ESCC cells with overexpression of Id1 or recombinant human IGF2 alone could promote esophageal fibroblasts to produce VEGF in vitro, and co-expression of shIGF2 or neutralizing antibody against IGF2 greatly diminished this effect. We also found that the CM collected from IGF2-activated fibroblasts could enhance the proliferation, tube-formation and migration abilities of human umbilical vein endothelial cells (HUVECs). The addition of VEGF-neutralizing antibody effectively attenuated these stimulatory effects. In addition, our results showed that the CM collected from IGF2-activated fibroblasts increased the mobility of VEGFR1+ bone marrow cells. Furthermore, data from in vivo experiment showed that bone marrow cells harvested from nude mice bearing Id1-expressing tumor xenografts had tumor-promoting activity when co-injected subcutaneously with untransfected ESCC cells into new groups of nude mice. CONCLUSIONS: Id1-overexpressing ESCC cells secrete IGF2 and educate stromal fibroblasts to secrete VEGF, which may in turn activate and mobilize endothelial cells as well as bone marrow-derived hematopoietic-progenitor cells to promote tumor angiogenesis.-
dc.languageengen_US
dc.publisherPergamon. The Journal's web site is located at http://www.elsevier.com/locate/ejca-
dc.relation.ispartofEuropean Journal of Canceren_US
dc.subjectMedical sciences-
dc.subjectOncology-
dc.titleRole of Id1-IGF2-VEGF-VEGFR relay in esophageal tumorigenesisen_US
dc.typeConference_Paperen_US
dc.identifier.emailCheung, ALM: lmcheung@hku.hken_US
dc.identifier.emailLi, B: libinhku@hkucc.hku.hken_US
dc.identifier.emailTsao, SW: gswtsao@hku.hken_US
dc.identifier.emailChan, KW: hrmtckw@hku.hken_US
dc.identifier.authorityCheung, ALM=rp00332en_US
dc.identifier.doi10.1016/S0959-8049(14)50134-7-
dc.identifier.hkuros234326en_US
dc.identifier.volume50en_US
dc.identifier.issuesuppl. 5-
dc.identifier.spageS35, abstract no. 161en_US
dc.identifier.epageS36en_US
dc.publisher.placeUnited Kingdom-

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