TY  - JOUR
A1  - Upcin, Berin
A1  - Henke, Erik
A1  - Kleefeldt, Florian
A1  - Hoffmann, Helene
A1  - Rosenwald, Andreas
A1  - Irmak-Sav, Ster
A1  - Aktas, Huseyin Bertal
A1  - Rückschloß, Uwe
A1  - Ergün, Süleyman
T1  - Contribution of adventitia-derived stem and progenitor cells to new vessel formation in tumors
T2  - Cells
N2  - 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, 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.
KW  - vascularization model
KW  - tumor spheroids
KW  - vascular wall stem and progenitor cells
KW  - aortic adventitia
KW  - vasculogenesis
KW  - tumor-vessel wall-interface model
Y1  - 2021
UR  - https://opus.bibliothek.uni-wuerzburg.de/frontdoor/index/index/docId/24257
UR  - https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-242577
VL  - 10
IS  - 7
ER  -