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Article: Targeting VEGFR-1 and VEGFR2-expressing non-tumor cells is essential for esophageal cancer therapy

TitleTargeting VEGFR-1 and VEGFR2-expressing non-tumor cells is essential for esophageal cancer therapy
Authors
KeywordsTumor angiogenesis
Bone marrow-derived cells
Tumor microenvironment
VEGF receptors
Antibody therapy
Issue Date2015
PublisherImpact Journals LLC. The Journal's web site is located at http://www.impactjournals.com/oncotarget/index.html
Citation
Oncotarget, 2015, v. 6 n. 3, p. 1790-1805 How to Cite?
AbstractIncreasing appreciation of tumor heterogeneity and the tumor-host interaction has stimulated interest in developing novel therapies that target both tumor cells and tumor microenvironment. Bone marrow derived cells (BMDCs) constitute important components of the tumor microenvironment. In this study, we aim to investigate the significance of VEGFR1- and VEGFR2-expressing non-tumor cells, including BMDCs, in esophageal cancer (EC) progression and in VEGFR1/VEGFR2-targeted therapies. Here we report that VEGFR1 or VEGFR2 blockade can significantly attenuate VEGF-induced Src and Erk signaling, as well as the proliferation and migration of VEGFR1+ and VEGFR2+ bone marrow cells and their pro-invasive effect on cancer cells. Importantly, our in vivo data show for the first time that systemic blockade of VEGFR1+ or VEGFR2+ non-tumor cells with neutralizing antibodies is sufficient to significantly suppress esophageal tumor growth, angiogenesis and metastasis in mice. Moreover, our tissue microarray study of human EC clinical specimens showed the clinicopathological significance of VEGFR1 and VEGFR2 in EC, which suggest that anti-VEGFR1/VEGFR2 therapies may be particularly beneficial for patients with aggressive EC. In conclusion, this study demonstrates the important contributions of VEGFR1+ and VEGFR2+ non-tumor cells in esophageal cancer progression, and substantiates the validity of these receptors as therapeutic targets for this deadly disease.
Persistent Identifierhttp://hdl.handle.net/10722/208679
ISSN
2015 Impact Factor: 5.008
2015 SCImago Journal Rankings: 2.294
PubMed Central ID

 

DC FieldValueLanguage
dc.contributor.authorXu, WW-
dc.contributor.authorLi, B-
dc.contributor.authorLam, AKY-
dc.contributor.authorTsao, GSW-
dc.contributor.authorLaw, SYK-
dc.contributor.authorChan, KW-
dc.contributor.authorYuan, QJ-
dc.contributor.authorCheung, ALM-
dc.date.accessioned2015-03-18T09:03:22Z-
dc.date.available2015-03-18T09:03:22Z-
dc.date.issued2015-
dc.identifier.citationOncotarget, 2015, v. 6 n. 3, p. 1790-1805-
dc.identifier.issn1949-2553-
dc.identifier.urihttp://hdl.handle.net/10722/208679-
dc.description.abstractIncreasing appreciation of tumor heterogeneity and the tumor-host interaction has stimulated interest in developing novel therapies that target both tumor cells and tumor microenvironment. Bone marrow derived cells (BMDCs) constitute important components of the tumor microenvironment. In this study, we aim to investigate the significance of VEGFR1- and VEGFR2-expressing non-tumor cells, including BMDCs, in esophageal cancer (EC) progression and in VEGFR1/VEGFR2-targeted therapies. Here we report that VEGFR1 or VEGFR2 blockade can significantly attenuate VEGF-induced Src and Erk signaling, as well as the proliferation and migration of VEGFR1+ and VEGFR2+ bone marrow cells and their pro-invasive effect on cancer cells. Importantly, our in vivo data show for the first time that systemic blockade of VEGFR1+ or VEGFR2+ non-tumor cells with neutralizing antibodies is sufficient to significantly suppress esophageal tumor growth, angiogenesis and metastasis in mice. Moreover, our tissue microarray study of human EC clinical specimens showed the clinicopathological significance of VEGFR1 and VEGFR2 in EC, which suggest that anti-VEGFR1/VEGFR2 therapies may be particularly beneficial for patients with aggressive EC. In conclusion, this study demonstrates the important contributions of VEGFR1+ and VEGFR2+ non-tumor cells in esophageal cancer progression, and substantiates the validity of these receptors as therapeutic targets for this deadly disease.-
dc.languageeng-
dc.publisherImpact Journals LLC. The Journal's web site is located at http://www.impactjournals.com/oncotarget/index.html-
dc.relation.ispartofOncotarget-
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subjectTumor angiogenesis-
dc.subjectBone marrow-derived cells-
dc.subjectTumor microenvironment-
dc.subjectVEGF receptors-
dc.subjectAntibody therapy-
dc.titleTargeting VEGFR-1 and VEGFR2-expressing non-tumor cells is essential for esophageal cancer therapy-
dc.typeArticle-
dc.identifier.emailLi, B: libinhku@hkucc.hku.hk-
dc.identifier.emailTsao, GSW: gswtsao@hku.hk-
dc.identifier.emailLaw, SYK: slaw@hku.hk-
dc.identifier.emailChan, KW: hrmtckw@hku.hk-
dc.identifier.emailYuan, QJ: qiuju@graduate.hku.hk-
dc.identifier.emailCheung, ALM: lmcheung@hku.hk-
dc.identifier.authorityTsao, GSW=rp00399-
dc.identifier.authorityLaw, SYK=rp00437-
dc.identifier.authorityChan, KW=rp00330-
dc.identifier.authorityCheung, ALM=rp00332-
dc.description.naturepublished_or_final_version-
dc.identifier.pmid25595897-
dc.identifier.pmcidPMC4359332-
dc.identifier.hkuros242533-
dc.identifier.hkuros244179-
dc.identifier.volume6-
dc.identifier.issue3-
dc.identifier.spage1790-
dc.identifier.epage1805-
dc.publisher.placeUnited States-

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