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An Integrated Gene Expression Landscape Profiling Approach to Identify Lung Tumor Endothelial Cell Heterogeneity and Angiogenic Candidates.
Goveia, Jermaine; Rohlenova, Katerina; Taverna, Federico; Treps, Lucas; Conradi, Lena-Christin; Pircher, Andreas; Geldhof, Vincent; de Rooij, Laura P M H; Kalucka, Joanna; Sokol, Liliana; García-Caballero, Melissa; Zheng, Yingfeng; Qian, Junbin; Teuwen, Laure-Anne; Khan, Shawez; Boeckx, Bram; Wauters, Els; Decaluwé, Herbert; De Leyn, Paul; Vansteenkiste, Johan; Weynand, Birgit; Sagaert, Xavier; Verbeken, Erik; Wolthuis, Albert; Topal, Baki; Everaerts, Wouter; Bohnenberger, Hanibal; Emmert, Alexander; Panovska, Dena; De Smet, Frederik; Staal, Frank J T; Mclaughlin, Rene J; Impens, Francis; Lagani, Vincenzo; Vinckier, Stefan; Mazzone, Massimiliano; Schoonjans, Luc; Dewerchin, Mieke; Eelen, Guy; Karakach, Tobias K; Yang, Huanming; Wang, Jian; Bolund, Lars; Lin, Lin; Thienpont, Bernard; Li, Xuri; Lambrechts, Diether; Luo, Yonglun; Carmeliet, Peter.
Affiliation
  • Goveia J; Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology and Leuven Cancer Institute (LKI), KU Leuven, VIB Center for Cancer Biology, Leuven 3000, Belgium.
  • Rohlenova K; Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology and Leuven Cancer Institute (LKI), KU Leuven, VIB Center for Cancer Biology, Leuven 3000, Belgium.
  • Taverna F; Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology and Leuven Cancer Institute (LKI), KU Leuven, VIB Center for Cancer Biology, Leuven 3000, Belgium.
  • Treps L; Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology and Leuven Cancer Institute (LKI), KU Leuven, VIB Center for Cancer Biology, Leuven 3000, Belgium.
  • Conradi LC; Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology and Leuven Cancer Institute (LKI), KU Leuven, VIB Center for Cancer Biology, Leuven 3000, Belgium.
  • Pircher A; Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology and Leuven Cancer Institute (LKI), KU Leuven, VIB Center for Cancer Biology, Leuven 3000, Belgium.
  • Geldhof V; Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology and Leuven Cancer Institute (LKI), KU Leuven, VIB Center for Cancer Biology, Leuven 3000, Belgium.
  • de Rooij LPMH; Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology and Leuven Cancer Institute (LKI), KU Leuven, VIB Center for Cancer Biology, Leuven 3000, Belgium.
  • Kalucka J; Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology and Leuven Cancer Institute (LKI), KU Leuven, VIB Center for Cancer Biology, Leuven 3000, Belgium.
  • Sokol L; Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology and Leuven Cancer Institute (LKI), KU Leuven, VIB Center for Cancer Biology, Leuven 3000, Belgium.
  • García-Caballero M; Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology and Leuven Cancer Institute (LKI), KU Leuven, VIB Center for Cancer Biology, Leuven 3000, Belgium.
  • Zheng Y; State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou 510060, Guangdong, China.
  • Qian J; Laboratory of Translational Genetics, Department of Oncology and Leuven Cancer Institute (LKI), KU Leuven, VIB Center for Cancer Biology, Leuven 3000, Belgium.
  • Teuwen LA; Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology and Leuven Cancer Institute (LKI), KU Leuven, VIB Center for Cancer Biology, Leuven 3000, Belgium.
  • Khan S; Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology and Leuven Cancer Institute (LKI), KU Leuven, VIB Center for Cancer Biology, Leuven 3000, Belgium.
  • Boeckx B; Laboratory of Translational Genetics, Department of Oncology and Leuven Cancer Institute (LKI), KU Leuven, VIB Center for Cancer Biology, Leuven 3000, Belgium.
  • Wauters E; Respiratory Oncology Unit (Respiratory Medicine) and Leuven Lung Cancer Group, University Hospitals Leuven, Leuven 3000, Belgium.
  • Decaluwé H; 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.
  • De Leyn P; 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.
  • Vansteenkiste J; Respiratory Oncology Unit (Respiratory Medicine) and Leuven Lung Cancer Group, University Hospitals Leuven, Leuven 3000, Belgium.
  • Weynand B; Translational Cell & Tissue Research, Department of Imaging & Pathology, KU Leuven, Leuven 3000, Belgium.
  • Sagaert X; Translational Cell & Tissue Research, Department of Imaging & Pathology, KU Leuven, Leuven 3000, Belgium.
  • Verbeken E; Translational Cell & Tissue Research, Department of Imaging & Pathology, KU Leuven, Leuven 3000, Belgium.
  • Wolthuis A; Department of Abdominal Surgery, University Hospitals Leuven, Leuven 3000, Belgium.
  • Topal B; Department of Abdominal Surgery, University Hospitals Leuven, Leuven 3000, Belgium.
  • Everaerts W; Laboratory for Experimental Urology, Department of Development and Regeneration, KU Leuven, Leuven 3000, Belgium; Department of Urology, University Hospitals Leuven, Leuven 3000, Belgium.
  • Bohnenberger H; Institute of Pathology, University Medical Center, Göttingen 37075, Germany.
  • Emmert A; Department of Thoracic and Cardiovascular Surgery, University Medical Center, Göttingen 37075, Germany.
  • Panovska D; Laboratory for Precision Cancer Medicine, Translational Cell & Tissue Research, Department of Imaging & Pathology, KU Leuven, Leuven 3000, Belgium.
  • De Smet F; Laboratory for Precision Cancer Medicine, Translational Cell & Tissue Research, Department of Imaging & Pathology, KU Leuven, Leuven 3000, Belgium.
  • Staal FJT; Department of Immunology and Blood Transfusion, Leiden University Medical Center, Leiden 2300 RC, the Netherlands.
  • Mclaughlin RJ; Department of Immunology and Blood Transfusion, Leiden University Medical Center, Leiden 2300 RC, the Netherlands.
  • Impens F; VIB Proteomics Core and VIB Center for Medical Biotechnology, Ghent 9000, Belgium; Department of Biomolecular Medicine, Ghent University, Ghent 9000, Belgium.
  • Lagani V; Institute of Chemical Biology, Ilia State University, Tbilisi 0162, Georgia; Gnosis Data Analysis PC, Heraklion GR-700 13, Greece.
  • Vinckier S; Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology and Leuven Cancer Institute (LKI), KU Leuven, VIB Center for Cancer Biology, Leuven 3000, Belgium.
  • Mazzone M; Laboratory of Tumor Inflammation and Angiogenesis, Department of Oncology and Leuven Cancer Institute (LKI), KU Leuven, VIB Center for Cancer Biology, Leuven 3000, Belgium.
  • Schoonjans L; Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology and Leuven Cancer Institute (LKI), KU Leuven, VIB Center for Cancer Biology, Leuven 3000, Belgium.
  • Dewerchin M; Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology and Leuven Cancer Institute (LKI), KU Leuven, VIB Center for Cancer Biology, Leuven 3000, Belgium.
  • Eelen G; Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology and Leuven Cancer Institute (LKI), KU Leuven, VIB Center for Cancer Biology, Leuven 3000, Belgium.
  • Karakach TK; Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology and Leuven Cancer Institute (LKI), KU Leuven, VIB Center for Cancer Biology, Leuven 3000, Belgium.
  • Yang H; BGI-Shenzhen, Shenzhen 518083, China; China National GeneBank, BGI-Shenzhen, Shenzhen 518120, China.
  • Wang J; BGI-Shenzhen, Shenzhen 518083, China; China National GeneBank, BGI-Shenzhen, Shenzhen 518120, China.
  • Bolund L; Department of Biomedicine, Aarhus University, Aarhus 8000, Denmark; Lars Bolund Institute of Regenerative Medicine, BGI-Qingdao, Qingdao 266555, China.
  • Lin L; Department of Biomedicine, Aarhus University, Aarhus 8000, Denmark; Lars Bolund Institute of Regenerative Medicine, BGI-Qingdao, Qingdao 266555, China.
  • Thienpont B; Laboratory for Functional Epigenetics, Department of Human Genetics, KU Leuven, Leuven 3000, Belgium.
  • Li X; State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou 510060, Guangdong, China. Electronic address: lixr6@mail.sysu.edu.cn.
  • Lambrechts D; Laboratory of Translational Genetics, Department of Oncology and Leuven Cancer Institute (LKI), KU Leuven, VIB Center for Cancer Biology, Leuven 3000, Belgium.
  • Luo Y; BGI-Shenzhen, Shenzhen 518083, China; China National GeneBank, BGI-Shenzhen, Shenzhen 518120, China; Department of Biomedicine, Aarhus University, Aarhus 8000, Denmark; Lars Bolund Institute of Regenerative Medicine, BGI-Qingdao, Qingdao 266555, China. Electronic address: alun@biomed.au.dk.
  • Carmeliet P; Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology and Leuven Cancer Institute (LKI), KU Leuven, VIB Center for Cancer Biology, Leuven 3000, Belgium; State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou 510060, Guangdong, China
Cancer Cell ; 37(1): 21-36.e13, 2020 01 13.
Article in En | MEDLINE | ID: mdl-31935371
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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Gene Expression Regulation, Neoplastic / Gene Expression Profiling / Endothelial Cells / Lung Neoplasms / Neovascularization, Pathologic Type of study: Prognostic_studies Limits: Animals / Female / Humans / Male Language: En Journal: Cancer Cell Journal subject: NEOPLASIAS Year: 2020 Document type: Article Affiliation country: Belgium Country of publication: United States

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Gene Expression Regulation, Neoplastic / Gene Expression Profiling / Endothelial Cells / Lung Neoplasms / Neovascularization, Pathologic Type of study: Prognostic_studies Limits: Animals / Female / Humans / Male Language: En Journal: Cancer Cell Journal subject: NEOPLASIAS Year: 2020 Document type: Article Affiliation country: Belgium Country of publication: United States