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PlGF-induced VEGFR1...
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Iwamoto, HidekiKarolinska Inst, Sweden
(författare)
PlGF-induced VEGFR1-dependent vascular remodeling determines opposing antitumor effects and drug resistance to Dll4-Notch inhibitors
- Artikel/kapitelEngelska2015
Förlag, utgivningsår, omfång ...
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AMER ASSOC ADVANCEMENT SCIENCE,2015
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electronicrdacarrier
Nummerbeteckningar
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LIBRIS-ID:oai:DiVA.org:liu-145073
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https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-145073URI
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https://doi.org/10.1126/sciadv.1400244DOI
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http://kipublications.ki.se/Default.aspx?queryparsed=id:136560524URI
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Språk:engelska
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Sammanfattning på:engelska
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Ämneskategori:art swepub-publicationtype
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Funding Agencies|Swedish Research Council; Swedish Cancer Foundation; Karolinska Institute Foundation; Karolinska Institute distinguished professor award; Torsten Soderberg Foundation; European Research Council (ERC) [250021]; NOVO Nordisk Foundation; Royal Alice Wallenberg Foundation; International Research Fund for Subsidy of Kyushu University School of Medicine Alumni
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Inhibition of Dll4 (delta-like ligand 4)-Notch signaling-mediated tumor angiogenesis is an attractive approach in cancer therapy. However, inhibition of Dll4-Notch signaling has produced different effects in various tumors, and no biomarkers are available for predicting the anti-Dll4-Notch-associated antitumor activity. We show that human and mouse tumor cell-derived placental growth factor (PlGF) is a key determinant of the Dll4-Notch-induced vascular remodeling and tumor growth. In natural PlGF-expressing human tumors, inhibition of Dll4-Notch signaling markedly accelerated tumor growth by increasing blood perfusion in nonleaking tumor vasculatures. Conversely, in PlGF-negative tumors, Dll4 inhibition suppressed tumor growth by the formation of nonproductive and leaky vessels. Surprisingly, genetic inactivation of vascular endothelial growth factor receptor 1 (VEGFR1) completely abrogated the PlGF-modulated vascular remodeling and tumor growth, indicating a crucial role for VEGFR1-mediated signals in modulating Dll4-Notch functions. These findings provide mechanistic insights on PlGF-VEGFR1 signaling in the modulation of the Dll4-Notch pathway in angiogenesis and tumor growth, and have therapeutic implications of PlGF as a biomarker for predicting the antitumor benefits of Dll4 and Notch inhibitors.
Ämnesord och genrebeteckningar
Biuppslag (personer, institutioner, konferenser, titlar ...)
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Zhang, YinKarolinska Institutet,Karolinska Inst, Sweden
(författare)
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Seki, TakahiroKarolinska Institutet,Karolinska Inst, Sweden
(författare)
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Yang, YunlongKarolinska Institutet,Karolinska Inst, Sweden
(författare)
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Nakamura, MasakiKarolinska Institutet,Karolinska Inst, Sweden
(författare)
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Wang, JianKarolinska Inst, Sweden
(författare)
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Yang, XiaojuanKarolinska Inst, Sweden; Tongji Univ, Peoples R China
(författare)
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Torimura, TakujiKurume Univ, Japan
(författare)
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Cao, YihaiLinköpings universitet,Institutionen för medicin och hälsa,Medicinska fakulteten,Karolinska Inst, Sweden; Univ Leicester, England; Glenfield Hosp, England(Swepub:liu)yihca64
(författare)
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Karolinska InstitutetKarolinska Inst, Sweden
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:Science Advances: AMER ASSOC ADVANCEMENT SCIENCE1:32375-2548
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