Contribution of adventitia-derived stem and progenitor cells to new vessel formation in tumors

Please always quote using this URN: urn:nbn:de:bvb:20-opus-242577
  • Blocking 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, weBlocking 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.show moreshow less

Download full text files

Export metadata

Additional Services

Share in Twitter Search Google Scholar Statistics
Metadaten
Author: Berin UpcinORCiD, Erik HenkeORCiD, Florian Kleefeldt, Helene Hoffmann, Andreas Rosenwald, Ster Irmak-Sav, Huseyin Bertal Aktas, Uwe Rückschloß, Süleyman Ergün
URN:urn:nbn:de:bvb:20-opus-242577
Document Type:Journal article
Faculties:Medizinische Fakultät / Pathologisches Institut
Medizinische Fakultät / Institut für Anatomie und Zellbiologie
Language:English
Parent Title (English):Cells
Year of Completion:2021
Volume:10
Issue:7
Article Number:1719
Source:Cells (2021) 10(7):1719. DOI: 10.3390/cells10071719
DOI:https://doi.org/10.3390/cells10071719
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Tag:aortic adventitia; tumor spheroids; tumor-vessel wall-interface model; vascular wall stem and progenitor cells; vascularization model; vasculogenesis
Release Date:2021/09/10
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International