Institut for Biomedicin

Lars Bolund

An Integrated Gene Expression Landscape Profiling Approach to Identify Lung Tumor Endothelial Cell Heterogeneity and Angiogenic Candidates

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DOI

  • Jermaine Goveia, Laboratory of Angiogenesis and Vascular Metabolism, VIB Center for Cancer Biology (CCB), VIB, 3000 Leuven, Belgium; Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology and Leuven Cancer Institute (LKI), KU Leuven, 3000 Leuven, Belgium.
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  • Katerina Rohlenova, Laboratory of Angiogenesis and Vascular Metabolism, VIB Center for Cancer Biology (CCB), VIB, 3000 Leuven, Belgium; Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology and Leuven Cancer Institute (LKI), KU Leuven, 3000 Leuven, Belgium.
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  • Federico Taverna, Laboratory of Angiogenesis and Vascular Metabolism, VIB Center for Cancer Biology (CCB), VIB, 3000 Leuven, Belgium; Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology and Leuven Cancer Institute (LKI), KU Leuven, 3000 Leuven, Belgium.
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  • Lucas Treps, Laboratory of Angiogenesis and Vascular Metabolism, VIB Center for Cancer Biology (CCB), VIB, 3000 Leuven, Belgium; Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology and Leuven Cancer Institute (LKI), KU Leuven, 3000 Leuven, Belgium.
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  • Lena-Christin Conradi, Laboratory of Angiogenesis and Vascular Metabolism, VIB Center for Cancer Biology (CCB), VIB, 3000 Leuven, Belgium; Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology and Leuven Cancer Institute (LKI), KU Leuven, 3000 Leuven, Belgium.
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  • Andreas Pircher, Laboratory of Angiogenesis and Vascular Metabolism, VIB Center for Cancer Biology (CCB), VIB, 3000 Leuven, Belgium; Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology and Leuven Cancer Institute (LKI), KU Leuven, 3000 Leuven, Belgium.
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  • Vincent Geldhof, Laboratory of Angiogenesis and Vascular Metabolism, VIB Center for Cancer Biology (CCB), VIB, 3000 Leuven, Belgium; Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology and Leuven Cancer Institute (LKI), KU Leuven, 3000 Leuven, Belgium.
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  • Laura P M H de Rooij, Laboratory of Angiogenesis and Vascular Metabolism, VIB Center for Cancer Biology (CCB), VIB, 3000 Leuven, Belgium; Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology and Leuven Cancer Institute (LKI), KU Leuven, 3000 Leuven, Belgium.
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  • Joanna Kalucka
  • Liliana Sokol, Laboratory of Angiogenesis and Vascular Metabolism, VIB Center for Cancer Biology (CCB), VIB, 3000 Leuven, Belgium; Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology and Leuven Cancer Institute (LKI), KU Leuven, 3000 Leuven, Belgium.
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  • Melissa García-Caballero, Laboratory of Angiogenesis and Vascular Metabolism, VIB Center for Cancer Biology (CCB), VIB, 3000 Leuven, Belgium; Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology and Leuven Cancer Institute (LKI), KU Leuven, 3000 Leuven, Belgium.
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  • Yingfeng Zheng, State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou 510060, Guangdong, P.R. China.
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  • Junbin Qian, Laboratory of Translational Genetics, Department of Oncology and Leuven Cancer Institute (LKI), KU Leuven, 3000 Leuven, Belgium; Laboratory of Translational Genetics, VIB Center for Cancer Biology (CCB), VIB, 3000 Leuven, Belgium.
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  • Laure-Anne Teuwen, Laboratory of Angiogenesis and Vascular Metabolism, VIB Center for Cancer Biology (CCB), VIB, 3000 Leuven, Belgium; Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology and Leuven Cancer Institute (LKI), KU Leuven, 3000 Leuven, Belgium.
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  • Shawez Khan, Laboratory of Angiogenesis and Vascular Metabolism, VIB Center for Cancer Biology (CCB), VIB, 3000 Leuven, Belgium; Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology and Leuven Cancer Institute (LKI), KU Leuven, 3000 Leuven, Belgium.
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  • Bram Boeckx, Laboratory of Translational Genetics, Department of Oncology and Leuven Cancer Institute (LKI), KU Leuven, 3000 Leuven, Belgium; Laboratory of Translational Genetics, VIB Center for Cancer Biology (CCB), VIB, 3000 Leuven, Belgium.
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  • Els Wauters, Respiratory Oncology Unit (Respiratory Medicine) and Leuven Lung Cancer Group, University Hospitals Leuven, Leuven 3000, Belgium.
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  • Herbert Decaluwé, Respiratory Oncology Unit (Respiratory Medicine) and Leuven Lung Cancer Group, University Hospitals Leuven, Leuven 3000, Belgium; Department of Thoracic Surgery, University Hospitals Leuven, Leuven 3000, Belgium.
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  • Paul De Leyn, Respiratory Oncology Unit (Respiratory Medicine) and Leuven Lung Cancer Group, University Hospitals Leuven, Leuven 3000, Belgium; Department of Thoracic Surgery, University Hospitals Leuven, Leuven 3000, Belgium.
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  • Johan Vansteenkiste, Respiratory Oncology Unit (Respiratory Medicine) and Leuven Lung Cancer Group, University Hospitals Leuven, Leuven 3000, Belgium.
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  • Birgit Weynand, Translational Cell & Tissue Research, Department of Imaging & Pathology, KU Leuven, 3000 Leuven, Belgium.
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  • Xavier Sagaert, Translational Cell & Tissue Research, Department of Imaging & Pathology, KU Leuven, 3000 Leuven, Belgium.
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  • Erik Verbeken, Translational Cell & Tissue Research, Department of Imaging & Pathology, KU Leuven, 3000 Leuven, Belgium.
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  • Albert Wolthuis, Department of Abdominal Surgery, University Hospitals Leuven, Leuven 3000, Belgium.
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  • Baki Topal, Department of Abdominal Surgery, University Hospitals Leuven, Leuven 3000, Belgium.
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  • Wouter Everaert, Laboratory for Experimental Urology, Department of Development and Regeneration, KU Leuven, Leuven 3000, Belgium; Department of Urology, University Hospitals Leuven, Leuven 3000, Belgium.
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  • Hanibal Bohnenberger, Institute of Pathology, University Medical Center, Göttingen 37075, Germany.
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  • Alexander Emmert, Department of Thoracic and Cardiovascular Surgery, University Medical Center, Göttingen 37075, Germany.
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  • Dena Panovska, Laboratory for Precision Cancer Medicine, Translational Cell & Tissue Research, Department of Imaging & Pathology, KU Leuven, Leuven 3000, Belgium.
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  • Frederik De Smet, Laboratory for Precision Cancer Medicine, Translational Cell & Tissue Research, Department of Imaging & Pathology, KU Leuven, Leuven 3000, Belgium.
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  • Frank J T Staal, Department of Immunology and Blood Transfusion, Leiden University Medical Center, Leiden 2300 RC, the Netherlands.
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  • Rene J Mclaughlin, Department of Immunology and Blood Transfusion, Leiden University Medical Center, Leiden 2300 RC, the Netherlands.
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  • Francis Impens, VIB Proteomics Core and VIB Center for Medical Biotechnology, Ghent 9000, Belgium; Department of Biomolecular Medicine, Ghent University, Ghent 9000, Belgium.
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  • Vincenzo Lagani, Institute of Chemical Biology, Ilia State University, Tbilisi 0162, Georgia; Gnosis Data Analysis PC, Heraklion GR-700 13, Greece.
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  • Stefan Vinckier, Laboratory of Angiogenesis and Vascular Metabolism, VIB Center for Cancer Biology (CCB), VIB, 3000 Leuven, Belgium; Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology and Leuven Cancer Institute (LKI), KU Leuven, 3000 Leuven, Belgium.
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  • Massimiliano Mazzone, Laboratory of Tumor Inflammation and Angiogenesis, Department of Oncology and Leuven Cancer Institute (LKI), KU Leuven, VIB Center for Cancer Biology, Leuven 3000, Belgium.
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  • Luc Schoonjans, Laboratory of Angiogenesis and Vascular Metabolism, VIB Center for Cancer Biology (CCB), VIB, 3000 Leuven, Belgium; Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology and Leuven Cancer Institute (LKI), KU Leuven, 3000 Leuven, Belgium.
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  • Mieke Dewerchin, Laboratory of Angiogenesis and Vascular Metabolism, VIB Center for Cancer Biology (CCB), VIB, 3000 Leuven, Belgium; Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology and Leuven Cancer Institute (LKI), KU Leuven, 3000 Leuven, Belgium.
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  • Guy Eelen, Laboratory of Angiogenesis and Vascular Metabolism, VIB Center for Cancer Biology (CCB), VIB, 3000 Leuven, Belgium; Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology and Leuven Cancer Institute (LKI), KU Leuven, 3000 Leuven, Belgium.
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  • Tobias K Karakach, Laboratory of Angiogenesis and Vascular Metabolism, VIB Center for Cancer Biology (CCB), VIB, 3000 Leuven, Belgium; Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology and Leuven Cancer Institute (LKI), KU Leuven, 3000 Leuven, Belgium.
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  • Huanming Yang, BGI-Shenzhen, Shenzhen 518083, China; China National GeneBank, BGI-Shenzhen, Shenzhen 518120, China.
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  • Jian Wang, BGI-Shenzhen, Shenzhen 518083, China; China National GeneBank, BGI-Shenzhen, Shenzhen 518120, China.
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  • Lars Bolund
  • Lin Lin
  • Bernard Thienpont, Laboratory for Functional Epigenetics, Department of Human Genetics, KU Leuven, Leuven 3000, Belgium.
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  • Xuri Li, State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou 510060, Guangdong, P.R. China. Electronic address: lixr6@mail.sysu.edu.cn.
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  • Diether Lambrechts, Laboratory of Translational Genetics, Department of Oncology and Leuven Cancer Institute (LKI), KU Leuven, 3000 Leuven, Belgium; Laboratory of Translational Genetics, VIB Center for Cancer Biology (CCB), VIB, 3000 Leuven, Belgium.
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  • Yonglun Luo
  • Peter Carmeliet

Heterogeneity of lung tumor endothelial cell (TEC) phenotypes across patients, species (human/mouse), and models (in vivo/in vitro) remains poorly inventoried at the single-cell level. We single-cell RNA (scRNA)-sequenced 56,771 endothelial cells from human/mouse (peri)-tumoral lung and cultured human lung TECs, and detected 17 known and 16 previously unrecognized phenotypes, including TECs putatively regulating immune surveillance. We resolved the canonical tip TECs into a known migratory tip and a putative basement-membrane remodeling breach phenotype. Tip TEC signatures correlated with patient survival, and tip/breach TECs were most sensitive to vascular endothelial growth factor blockade. Only tip TECs were congruent across species/models and shared conserved markers. Integrated analysis of the scRNA-sequenced data with orthogonal multi-omics and meta-analysis data across different human tumors, validated by functional analysis, identified collagen modification as a candidate angiogenic pathway.

OriginalsprogEngelsk
TidsskriftCancer Cell
Vol/bind37
Nummer1
Sider (fra-til)21-36.e13
Antal sider29
ISSN1535-6108
DOI
StatusUdgivet - 2020

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