Tumor vessel co-option probed by single-cell analysis.


Journal

Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691

Informations de publication

Date de publication:
15 06 2021
Historique:
received: 18 10 2020
revised: 16 05 2021
accepted: 25 05 2021
entrez: 16 6 2021
pubmed: 17 6 2021
medline: 11 2 2022
Statut: ppublish

Résumé

Tumor 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.

Identifiants

pubmed: 34133923
pii: S2211-1247(21)00618-5
doi: 10.1016/j.celrep.2021.109253
pii:
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

109253

Informations de copyright

Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interest The authors declare no competing interests.

Auteurs

Laure-Anne Teuwen (LA)

Laboratory of Angiogenesis and Vascular Metabolism, Center for Cancer Biology (CCB), VIB, Department of Oncology, Leuven Cancer Institute, KU Leuven, Leuven 3000, Belgium; Translational Cancer Research Unit, GZA Hospitals Sint-Augustinus, Antwerp 2610, Belgium; Center for Oncological Research, University of Antwerp, Antwerp 2000, Belgium.

Laura P M H De Rooij (LPMH)

Laboratory of Angiogenesis and Vascular Metabolism, Center for Cancer Biology (CCB), VIB, Department of Oncology, Leuven Cancer Institute, KU Leuven, Leuven 3000, Belgium.

Anne Cuypers (A)

Laboratory of Angiogenesis and Vascular Metabolism, Center for Cancer Biology (CCB), VIB, Department of Oncology, Leuven Cancer Institute, KU Leuven, Leuven 3000, Belgium.

Katerina Rohlenova (K)

Laboratory of Angiogenesis and Vascular Metabolism, Center for Cancer Biology (CCB), VIB, Department of Oncology, Leuven Cancer Institute, KU Leuven, Leuven 3000, Belgium.

Sébastien J Dumas (SJ)

Laboratory of Angiogenesis and Vascular Metabolism, Center for Cancer Biology (CCB), VIB, Department of Oncology, Leuven Cancer Institute, KU Leuven, Leuven 3000, Belgium.

Melissa García-Caballero (M)

Laboratory of Angiogenesis and Vascular Metabolism, Center for Cancer Biology (CCB), VIB, Department of Oncology, Leuven Cancer Institute, KU Leuven, Leuven 3000, Belgium.

Elda Meta (E)

Laboratory of Angiogenesis and Vascular Metabolism, Center for Cancer Biology (CCB), VIB, Department of Oncology, Leuven Cancer Institute, KU Leuven, Leuven 3000, Belgium.

Jacob Amersfoort (J)

Laboratory of Angiogenesis and Vascular Metabolism, Center for Cancer Biology (CCB), VIB, Department of Oncology, Leuven Cancer Institute, KU Leuven, Leuven 3000, Belgium.

Federico Taverna (F)

Laboratory of Angiogenesis and Vascular Metabolism, Center for Cancer Biology (CCB), VIB, Department of Oncology, Leuven Cancer Institute, KU Leuven, Leuven 3000, Belgium.

Lisa M Becker (LM)

Laboratory of Angiogenesis and Vascular Metabolism, Center for Cancer Biology (CCB), VIB, Department of Oncology, Leuven Cancer Institute, KU Leuven, Leuven 3000, Belgium.

Nuphar Veiga (N)

Laboratory of Angiogenesis and Vascular Metabolism, Center for Cancer Biology (CCB), VIB, Department of Oncology, Leuven Cancer Institute, KU Leuven, Leuven 3000, Belgium.

Anna Rita Cantelmo (AR)

Laboratory of Angiogenesis and Vascular Metabolism, Center for Cancer Biology (CCB), VIB, Department of Oncology, Leuven Cancer Institute, KU Leuven, Leuven 3000, Belgium.

Vincent Geldhof (V)

Laboratory of Angiogenesis and Vascular Metabolism, Center for Cancer Biology (CCB), VIB, Department of Oncology, Leuven Cancer Institute, KU Leuven, Leuven 3000, Belgium.

Nadine V Conchinha (NV)

Laboratory of Angiogenesis and Vascular Metabolism, Center for Cancer Biology (CCB), VIB, Department of Oncology, Leuven Cancer Institute, KU Leuven, Leuven 3000, Belgium.

Joanna Kalucka (J)

Laboratory of Angiogenesis and Vascular Metabolism, Center for Cancer Biology (CCB), VIB, Department of Oncology, Leuven Cancer Institute, KU Leuven, Leuven 3000, Belgium.

Lucas Treps (L)

Laboratory of Angiogenesis and Vascular Metabolism, Center for Cancer Biology (CCB), VIB, Department of Oncology, Leuven Cancer Institute, KU Leuven, Leuven 3000, Belgium.

Lena-Christin Conradi (LC)

Laboratory of Angiogenesis and Vascular Metabolism, Center for Cancer Biology (CCB), VIB, Department of Oncology, Leuven Cancer Institute, KU Leuven, Leuven 3000, Belgium.

Shawez Khan (S)

Laboratory of Angiogenesis and Vascular Metabolism, Center for Cancer Biology (CCB), VIB, Department of Oncology, Leuven Cancer Institute, KU Leuven, Leuven 3000, Belgium.

Tobias K Karakach (TK)

Laboratory of Angiogenesis and Vascular Metabolism, Center for Cancer Biology (CCB), VIB, Department of Oncology, Leuven Cancer Institute, KU Leuven, Leuven 3000, Belgium.

Stefaan Soenen (S)

NanoHealth and Optical Imaging Group, Department of Imaging and Pathology, KU Leuven, Leuven 3000, Belgium.

Stefan Vinckier (S)

Laboratory of Angiogenesis and Vascular Metabolism, Center for Cancer Biology (CCB), VIB, Department of Oncology, Leuven Cancer Institute, KU Leuven, Leuven 3000, Belgium.

Luc Schoonjans (L)

Laboratory of Angiogenesis and Vascular Metabolism, Center for Cancer Biology (CCB), VIB, Department of Oncology, Leuven Cancer Institute, KU Leuven, Leuven 3000, Belgium; State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, 510275, Guangzhou, Guangdong, P.R. China.

Guy Eelen (G)

Laboratory of Angiogenesis and Vascular Metabolism, Center for Cancer Biology (CCB), VIB, Department of Oncology, Leuven Cancer Institute, KU Leuven, Leuven 3000, Belgium.

Steven Van Laere (S)

Translational Cancer Research Unit, GZA Hospitals Sint-Augustinus, Antwerp 2610, Belgium; Center for Oncological Research, University of Antwerp, Antwerp 2000, Belgium.

Mieke Dewerchin (M)

Laboratory of Angiogenesis and Vascular Metabolism, Center for Cancer Biology (CCB), VIB, Department of Oncology, Leuven Cancer Institute, KU Leuven, Leuven 3000, Belgium.

Luc Dirix (L)

Translational Cancer Research Unit, GZA Hospitals Sint-Augustinus, Antwerp 2610, Belgium; Center for Oncological Research, University of Antwerp, Antwerp 2000, Belgium.

Massimiliano Mazzone (M)

Laboratory of Tumor Inflammation and Angiogenesis, CCB, VIB, Department of Oncology, Leuven Cancer Institute, KU Leuven, Leuven 3000, Belgium.

Yonglun Luo (Y)

Department of Biomedicine, Aarhus University, Aarhus 8000, Denmark; Lars Bolund Institute of Regenerative Medicine, BGI-Qingdao, Qingdao 266555, P.R. China; BGI-Shenzhen, Shenzhen 518083, China; China National GeneBank, BGI-Shenzhen, Shenzhen 518120, P.R. China. Electronic address: alun@biomed.au.dk.

Peter Vermeulen (P)

Translational Cancer Research Unit, GZA Hospitals Sint-Augustinus, Antwerp 2610, Belgium; Center for Oncological Research, University of Antwerp, Antwerp 2000, Belgium.

Peter Carmeliet (P)

Laboratory of Angiogenesis and Vascular Metabolism, Center for Cancer Biology (CCB), VIB, Department of Oncology, Leuven Cancer Institute, KU Leuven, Leuven 3000, Belgium; State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, 510275, Guangzhou, Guangdong, P.R. China; Laboratory of Angiogenesis and Vascular Heterogeneity, Department of Biomedicine, Aarhus University, Aarhus 8000, Denmark. Electronic address: peter.carmeliet@kuleuven.be.

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