Cell Reports (Jun 2021)
Tumor vessel co-option probed by single-cell analysis
- Laure-Anne Teuwen,
- Laura P.M.H. De Rooij,
- Anne Cuypers,
- Katerina Rohlenova,
- Sébastien J. Dumas,
- Melissa García-Caballero,
- Elda Meta,
- Jacob Amersfoort,
- Federico Taverna,
- Lisa M. Becker,
- Nuphar Veiga,
- Anna Rita Cantelmo,
- Vincent Geldhof,
- Nadine V. Conchinha,
- Joanna Kalucka,
- Lucas Treps,
- Lena-Christin Conradi,
- Shawez Khan,
- Tobias K. Karakach,
- Stefaan Soenen,
- Stefan Vinckier,
- Luc Schoonjans,
- Guy Eelen,
- Steven Van Laere,
- Mieke Dewerchin,
- Luc Dirix,
- Massimiliano Mazzone,
- Yonglun Luo,
- Peter Vermeulen,
- Peter Carmeliet
Affiliations
- Laure-Anne Teuwen
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- NanoHealth and Optical Imaging Group, Department of Imaging and Pathology, KU Leuven, Leuven 3000, Belgium
- Stefan Vinckier
- 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
- 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
- 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
- Translational Cancer Research Unit, GZA Hospitals Sint-Augustinus, Antwerp 2610, Belgium; Center for Oncological Research, University of Antwerp, Antwerp 2000, Belgium
- Mieke Dewerchin
- 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
- Translational Cancer Research Unit, GZA Hospitals Sint-Augustinus, Antwerp 2610, Belgium; Center for Oncological Research, University of Antwerp, Antwerp 2000, Belgium
- Massimiliano Mazzone
- Laboratory of Tumor Inflammation and Angiogenesis, CCB, VIB, Department of Oncology, Leuven Cancer Institute, KU Leuven, Leuven 3000, Belgium
- Yonglun Luo
- 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; Corresponding author
- Peter Vermeulen
- Translational Cancer Research Unit, GZA Hospitals Sint-Augustinus, Antwerp 2610, Belgium; Center for Oncological Research, University of Antwerp, Antwerp 2000, Belgium
- Peter Carmeliet
- 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; Corresponding author
- Journal volume & issue
-
Vol. 35,
no. 11
p. 109253
Abstract
Summary: 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.
