Teuwen, Laure-AnneDe Rooij, Laura P M HCuypers, AnneRohlenova, KaterinaDumas, Sébastien JGarcía-Caballero, MelissaMeta, EldaAmersfoort, JacobTaverna, FedericoBecker, Lisa MVeiga, NupharCantelmo, Anna RitaGeldhof, VincentConchinha, Nadine VKalucka, JoannaTreps, LucasConradi, Lena-ChristinKhan, ShawezKarakach, Tobias KSoenen, StefaanVinckier, StefanSchoonjans, LucEelen, GuyVan Laere, StevenDewerchin, MiekeDirix, LucMazzone, MassimilianoLuo, YonglunVermeulen, PeterCarmeliet, Peter2025-01-072025-01-072021https://hdl.handle.net/10668/27805Tumor vessel co-option is poorly understood, yet it is a resistance mechanism against anti-angiogenic therapy (AAT). The heterogeneity of co-opted endothelial cells (ECs) and pericytes, co-opting cancer and myeloid cells in tumors growing via vessel co-option, has not been investigated at the single-cell level. Here, we use a murine AAT-resistant lung tumor model, in which VEGF-targeting induces vessel co-option for continued growth. Single-cell RNA sequencing (scRNA-seq) of 31,964 cells reveals, unexpectedly, a largely similar transcriptome of co-opted tumor ECs (TECs) and pericytes as their healthy counterparts. Notably, we identify cell types that might contribute to vessel co-option, i.e., an invasive cancer-cell subtype, possibly assisted by a matrix-remodeling macrophage population, and another M1-like macrophage subtype, possibly involved in keeping or rendering vascular cells quiescent.enAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/anti-angiogenic therapycancer cellsendothelial cellsmacrophagesmetastasispericytesresistancesingle-cell RNA sequencingtumor angiogenesistumor vessel co-optionAnimalsCell Line, TumorEndothelial CellsFemaleKidney NeoplasmsLung NeoplasmsMacrophagesMice, Inbred BALB CMyeloid CellsNeoplasmsPericytesSingle-Cell Analysisresearch article34133923open access10.1016/j.celrep.2021.1092532211-1247http://www.cell.com/article/S2211124721006185/pdf