Contribution of Adventitia-Derived Stem and Progenitor Cells to New Vessel Formation in Tumors

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dc.authoridHenke, Erik/0000-0003-2380-2682|Kleefeldt, Florian/0009-0007-7751-0403|Upcin, Berin/0000-0003-4853-9358
dc.authorwosidHenke, Erik/IAR-0413-2023
dc.contributor.authorUpcin, Berin
dc.contributor.authorHenke, Erik
dc.contributor.authorKleefeldt, Florian
dc.contributor.authorHoffmann, Helene
dc.contributor.authorRosenwald, Andreas
dc.contributor.authorIrmak-Sav, Ster
dc.contributor.authorAktas, Huseyin Bertal
dc.date.accessioned2024-07-18T20:50:42Z
dc.date.available2024-07-18T20:50:42Z
dc.date.issued2021
dc.departmentİstanbul Bilgi Üniversitesien_US
dc.description.abstractBlocking tumor vascularization has not yet come to fruition to the extent it was hoped for, as angiogenesis inhibitors have shown only partial success in the clinic. We hypothesized that under-appreciated vascular wall-resident stem and progenitor cells (VW-SPCs) might be involved in tumor vascularization and influence effectiveness of anti-angiogenic therapy. Indeed, in patient samples, we observed that vascular adventitia-resident CD34(+) VW-SPCs are recruited to tumors in situ from co-opted vessels. To elucidate this in detail, we established an ex vivo model using concomitant embedding of multi-cellular tumor spheroids (MCTS) and mouse aortic rings (ARs) into collagen gels, similar to the so-called aortic ring assay (ARA). Moreover, ARA was modified by removing the ARs' adventitia that harbors VW-SPCs. Thus, this model enabled distinguishing the contribution of VW-SPCs from that of mature endothelial cells (ECs) to new vessel formation. Our results show that the formation of capillary-like sprouts is considerably delayed, and their number and network formation were significantly reduced by removing the adventitia. Substituting iPSC-derived neural spheroids for MCTS resulted in distinct sprouting patterns that were also strongly influenced by the presence or absence of VW-SPCs, also underlying the involvement of these cells in non-pathological vascularization. Our data suggest that more comprehensive approaches are needed in order to block all of the mechanisms contributing to tumor vascularization.en_US
dc.description.sponsorshipDeutsche Forschungsgemeinschaft (DFG, German Research Foundation) [374031971-TRR 240]en_US
dc.description.sponsorshipThis research was funded by Deutsche Forschungsgemeinschaft (DFG, German Research Foundation), grant number 374031971-TRR 240 to S.E. and H.S. (A03).en_US
dc.identifier.doi10.3390/cells10071719
dc.identifier.issn2073-4409
dc.identifier.issue7en_US
dc.identifier.pmid34359889en_US
dc.identifier.scopus2-s2.0-85114067568en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.urihttps://doi.org/10.3390/cells10071719
dc.identifier.urihttps://hdl.handle.net/11411/8175
dc.identifier.volume10en_US
dc.identifier.wosWOS:000677181200001en_US
dc.identifier.wosqualityQ2en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherMdpien_US
dc.relation.ispartofCellsen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectVascularization Modelen_US
dc.subjectTumor Spheroidsen_US
dc.subjectVascular Wall Stem And Progenitor Cellsen_US
dc.subjectAortic Adventitiaen_US
dc.subjectVasculogenesisen_US
dc.subjectTumor-Vessel Wall-İnterface Modelen_US
dc.subjectVasculogenic Mimicryen_US
dc.subjectVascular Adventitiaen_US
dc.subjectAngiogenesisen_US
dc.subjectGrowthen_US
dc.subjectSpheroidsen_US
dc.subjectInductionen_US
dc.subjectCanceren_US
dc.subjectIdentificationen_US
dc.subjectChemokinesen_US
dc.subjectHierarchyen_US
dc.titleContribution of Adventitia-Derived Stem and Progenitor Cells to New Vessel Formation in Tumors
dc.typeArticle

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