Endothelial precursor cell-based therapy to target the pathologic angiogenesis and compensate tumor hypoxia

2016
journal article
article
29
dc.abstract.enHypoxia-inducing pathologies as cancer develop pathologic and inefficient angiogenesis which rules tumor facilitating microenvironment, a key target for therapy. As such, the putative ability of endothelial precursor cells (EPCs) to specifically home to hypoxic sites of neovascularization prompted to design optimized, site-specific, cell-mediated, drug-/gene-targeting approach. Thus, EPC lines were established from aorta–gonad–mesonephros (AGM) of murine 10.5 dpc and 11.5 dpc embryo when endothelial repertoire is completed. Lines representing early endothelial differentiation steps were selected: MAgEC10.5 and MagEC11.5. Distinct in maturation, they differently express VEGF receptors, VE-cadherin and chemokine/receptors. MAgEC11.5, more differentiated than MAgEC 10.5, displayed faster angiogenesis in vitro, different response to hypoxia and chemokines. Both MAgEC lines cooperated to tube-like formation with mature endothelial cells and invaded tumor spheroids through a vasculogenesis-like process. In vivo, both MAgEC-formed vessels established blood flow. Intravenously injected, both MAgECs invaded MatrigelTM-plugs and targeted tumors. Here we show that EPCs (MAgEC11.5) target tumor angiogenesis and allow local overexpression of hypoxia-driven soluble VEGF-receptor2 enabling drastic tumor growth reduction. We propose that such EPCs, able to target tumor angiogenesis, could act as therapeutic gene vehicles to inhibit tumor growth by vessel normalization resulting from tumor hypoxia alleviation.pl
dc.affiliationPion Prorektora ds. badań naukowych i funduszy strukturalnych : Małopolskie Centrum Biotechnologiipl
dc.affiliationWydział Biochemii, Biofizyki i Biotechnologii : Zakład Biotechnologii Medycznejpl
dc.contributor.authorCollet, Guillaumepl
dc.contributor.authorSzade, Krzysztof - 109224 pl
dc.contributor.authorNowak, Witold - 108796 pl
dc.contributor.authorKlimkiewicz, Krzysztof - 114597 pl
dc.contributor.authorEl Hafny-Rahbi, Bouchrapl
dc.contributor.authorSzczepanek, Karol - 137332 pl
dc.contributor.authorSugiyama, Daisukepl
dc.contributor.authorWeglarczyk, Kazimierzpl
dc.contributor.authorFoucault-Collet, Alexandrapl
dc.contributor.authorGuichard, Alanpl
dc.contributor.authorMazan, Andrzejpl
dc.contributor.authorNadim, Mahdipl
dc.contributor.authorFasani, Fabiennepl
dc.contributor.authorLamerant-Fayel, Nathaliepl
dc.contributor.authorGrillon, Catherinepl
dc.contributor.authorPetoud, Stéphanepl
dc.contributor.authorBeloeil, Jean-Claudepl
dc.contributor.authorJózkowicz, Alicja - 128541 pl
dc.contributor.authorDulak, Józef - 127818 pl
dc.contributor.authorKieda, Claudine - 255953 pl
dc.date.accessioned2016-04-11T08:54:44Z
dc.date.available2016-04-11T08:54:44Z
dc.date.issued2016pl
dc.date.openaccess0
dc.description.accesstimew momencie opublikowania
dc.description.number2pl
dc.description.physical345-357pl
dc.description.versionostateczna wersja wydawcy
dc.description.volume370pl
dc.identifier.doi10.1016/j.canlet.2015.11.008pl
dc.identifier.eissn1872-7980pl
dc.identifier.issn0304-3835pl
dc.identifier.projectROD UJ / Ppl
dc.identifier.urihttp://ruj.uj.edu.pl/xmlui/handle/item/23747
dc.languageengpl
dc.language.containerengpl
dc.rightsUdzielam licencji. Uznanie autorstwa - Użycie niekomercyjne - Bez utworów zależnych 4.0 Międzynarodowa*
dc.rights.licenceCC-BY-NC-ND
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/legalcode.pl*
dc.share.typeinne
dc.subject.enendothelial precursor cellspl
dc.subject.enpathologic angiogenesis/vasculogenesispl
dc.subject.entumor targetingpl
dc.subject.encell gene therapypl
dc.subtypeArticlepl
dc.titleEndothelial precursor cell-based therapy to target the pathologic angiogenesis and compensate tumor hypoxiapl
dc.title.journalCancer Letterspl
dc.typeJournalArticlepl
dspace.entity.typePublication
dc.abstract.enpl
Hypoxia-inducing pathologies as cancer develop pathologic and inefficient angiogenesis which rules tumor facilitating microenvironment, a key target for therapy. As such, the putative ability of endothelial precursor cells (EPCs) to specifically home to hypoxic sites of neovascularization prompted to design optimized, site-specific, cell-mediated, drug-/gene-targeting approach. Thus, EPC lines were established from aorta–gonad–mesonephros (AGM) of murine 10.5 dpc and 11.5 dpc embryo when endothelial repertoire is completed. Lines representing early endothelial differentiation steps were selected: MAgEC10.5 and MagEC11.5. Distinct in maturation, they differently express VEGF receptors, VE-cadherin and chemokine/receptors. MAgEC11.5, more differentiated than MAgEC 10.5, displayed faster angiogenesis in vitro, different response to hypoxia and chemokines. Both MAgEC lines cooperated to tube-like formation with mature endothelial cells and invaded tumor spheroids through a vasculogenesis-like process. In vivo, both MAgEC-formed vessels established blood flow. Intravenously injected, both MAgECs invaded MatrigelTM-plugs and targeted tumors. Here we show that EPCs (MAgEC11.5) target tumor angiogenesis and allow local overexpression of hypoxia-driven soluble VEGF-receptor2 enabling drastic tumor growth reduction. We propose that such EPCs, able to target tumor angiogenesis, could act as therapeutic gene vehicles to inhibit tumor growth by vessel normalization resulting from tumor hypoxia alleviation.
dc.affiliationpl
Pion Prorektora ds. badań naukowych i funduszy strukturalnych : Małopolskie Centrum Biotechnologii
dc.affiliationpl
Wydział Biochemii, Biofizyki i Biotechnologii : Zakład Biotechnologii Medycznej
dc.contributor.authorpl
Collet, Guillaume
dc.contributor.authorpl
Szade, Krzysztof - 109224
dc.contributor.authorpl
Nowak, Witold - 108796
dc.contributor.authorpl
Klimkiewicz, Krzysztof - 114597
dc.contributor.authorpl
El Hafny-Rahbi, Bouchra
dc.contributor.authorpl
Szczepanek, Karol - 137332
dc.contributor.authorpl
Sugiyama, Daisuke
dc.contributor.authorpl
Weglarczyk, Kazimierz
dc.contributor.authorpl
Foucault-Collet, Alexandra
dc.contributor.authorpl
Guichard, Alan
dc.contributor.authorpl
Mazan, Andrzej
dc.contributor.authorpl
Nadim, Mahdi
dc.contributor.authorpl
Fasani, Fabienne
dc.contributor.authorpl
Lamerant-Fayel, Nathalie
dc.contributor.authorpl
Grillon, Catherine
dc.contributor.authorpl
Petoud, Stéphane
dc.contributor.authorpl
Beloeil, Jean-Claude
dc.contributor.authorpl
Józkowicz, Alicja - 128541
dc.contributor.authorpl
Dulak, Józef - 127818
dc.contributor.authorpl
Kieda, Claudine - 255953
dc.date.accessioned
2016-04-11T08:54:44Z
dc.date.available
2016-04-11T08:54:44Z
dc.date.issuedpl
2016
dc.date.openaccess
0
dc.description.accesstime
w momencie opublikowania
dc.description.numberpl
2
dc.description.physicalpl
345-357
dc.description.version
ostateczna wersja wydawcy
dc.description.volumepl
370
dc.identifier.doipl
10.1016/j.canlet.2015.11.008
dc.identifier.eissnpl
1872-7980
dc.identifier.issnpl
0304-3835
dc.identifier.projectpl
ROD UJ / P
dc.identifier.uri
http://ruj.uj.edu.pl/xmlui/handle/item/23747
dc.languagepl
eng
dc.language.containerpl
eng
dc.rights*
Udzielam licencji. Uznanie autorstwa - Użycie niekomercyjne - Bez utworów zależnych 4.0 Międzynarodowa
dc.rights.licence
CC-BY-NC-ND
dc.rights.uri*
http://creativecommons.org/licenses/by-nc-nd/4.0/legalcode.pl
dc.share.type
inne
dc.subject.enpl
endothelial precursor cells
dc.subject.enpl
pathologic angiogenesis/vasculogenesis
dc.subject.enpl
tumor targeting
dc.subject.enpl
cell gene therapy
dc.subtypepl
Article
dc.titlepl
Endothelial precursor cell-based therapy to target the pathologic angiogenesis and compensate tumor hypoxia
dc.title.journalpl
Cancer Letters
dc.typepl
JournalArticle
dspace.entity.type
Publication
Affiliations

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