1. Tumor vessel co-option probed by single-cell analysis
- Author
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Steven Van Laere, Mieke Dewerchin, Lena-Christin Conradi, Peter Carmeliet, Anna Rita Cantelmo, Federico Taverna, Massimiliano Mazzone, Yonglun Luo, Stefan Vinckier, Stefaan J. Soenen, Nuphar Veiga, Tobias K. Karakach, Peter B. Vermeulen, Lucas Treps, Joanna Kalucka, Sébastien J. Dumas, Luc Dirix, Elda Meta, Shawez Khan, Vincent Geldhof, Guy Eelen, Laure-Anne Teuwen, Luc Schoonjans, Nadine V. Conchinha, Katerina Rohlenova, Lisa M. Becker, Anne Cuypers, Melissa García-Caballero, Laura P.M.H. de Rooij, Jacob Amersfoort, [Teuwen,LA, De Roji,PMH, Cuypers,A, Rohlenova,A, Dumas,SH, García-Caballero,M, Meta,E, Amersfoort,J, Taverna,F, Becker,LM, Veiga,N, Cantelmo,AR, Geldhof,V, Conchinha,NV, Kalucka,J, Treps,L, Conradi,LC, Khan,S, Karakach,TK, Vinckier,S, Schoonjans,L, Eelen,G, Dewerchin,M, Carmeliet,P] Laboratory of Angiogenesis and Vascular Metabolism, Center for Cancer Biology (CCB), VIB, Department of Oncology, Leuven Cancer Institute, KU Leuven, Leuven, Belgium. [Teuwen,LA, Van Laere,S, Dirix,L, Vermeulen,P] Translational Cancer Research Unit, GZA Hospitals Sint-Augustinus, Antwerp, Belgium. [Teuwen,LA, Vermeulen,P] Center for Oncological Research, University of Antwerp, Antwerp, Belgium. [Soenen,S] NanoHealth and Optical Imaging Group, Department of Imaging and Pathology, KU Leuven, Leuven, Belgium. [Schoonjans,L, Carmeliet,P] State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou, Guangdong, P.R. China. [Mazzone,M] Laboratory of Tumor Inflammation and Angiogenesis, CCB, VIB, Department of Oncology, Leuven Cancer Institute, KU Leuven, Leuven, Belgium. [Luo,Y] Department of Biomedicine, Aarhus University, Aarhus, Denmark. [Luo,Y] Lars Bolund Institute of Regenerative Medicine, BGI-Qingdao, Qingdao, P.R. China. [Luo,Y] BGI-Shenzhen, Shenzhen, China. [Luo,Y] China National GeneBank, BGI-Shenzhen, Shenzhen, P.R. China. [Carmeliet,P] Laboratory of Angiogenesis and Vascular Heterogeneity, Department of Biomedicine, Aarhus University, Aarhus, Denmark. [Rohlenova,K] Institute of Biotechnology of the Czech Academy of Sciences, Praha – za´ pad, Central Bohemia, Czechia. [García-Caballero,M] Department of Molecular Biology and Biochemistry, Faculty of Sciences, and IBIMA (Biomedical Research Institute of Málaga), University of Málaga, Andalucía Tech, Málaga, Spain. [Cantelmo,AR] Laboratory of Cell Physiology, Lille University, Villeneuve d’Ascq, France. [Kalucka,J] Aarhus Institute of Advanced Studies (AIAS), Department of Biomedicine, Aarhus University, Aarhus, Denmark. [Conradi,LC] Clinic of General, Visceral and Pediatric Surgery, University Medical Center Göttingen, Göttingen, Germany. [Khan,S] National Center for Cancer Immune Therapy (CCIT-DK), Department of Oncology, Copenhagen University Hospital, Herlev, Denmark. [Karakach,TK] Bioinformatics Core Laboratory, Children’s Hospital Research Institute of Manitoba, Winnipeg, Canada. [Karakach,TK] Rady Faculty of Health Sciences, Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, Manitoba Canada., L.-A.T., L.D., S.V.L., and P.V. are supported by Fonds Oncologie Augustinus-Koning Boudewijnstichting and GZA Ziekenhuizen, A.C., K.R., N.V.C., L.P.M.H.d.R., and L.T. by the Fonds Wetenschappelijk Onderzoek (FWO), S.J.D. by a Marie Curie-IEF fellowship, V.G. by Strategisch Basisonderzoek FWO (SB-FWO), Y.L. by BGI-Research, Danish Research Council for Independent Research (DFF-1337-00128), Sapere Aude Young Research Talent Prize (DFF-1335–00763A), and Aarhus University Strategic Grant (AU-iCRISPR), and and P.C. by Methusalem funding (Flemish government), Fund for Scientific Research-Flanders (FWO-Vlaanderen), Foundation Against Cancer (2016-078), Kom op tegen Kanker (Stand up to Cancer, Flemish Cancer Society), European Research Council (ERC Proof of Concept grant ERC-713758 and Advanced ERC Research grant EU-ERC743074), and a NNF Laureate Research Grant from Novo Nordisk Foundation (NNF19OC0055802).
- Subjects
Anatomy::Cells::Cells, Cultured::Cell Line::Cell Line, Tumor [Medical Subject Headings] ,0301 basic medicine ,Lung Neoplasms ,Diseases::Neoplasms::Neoplasms by Site::Urogenital Neoplasms::Urologic Neoplasms::Kidney Neoplasms [Medical Subject Headings] ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Cytological Techniques::Single-Cell Analysis [Medical Subject Headings] ,Vascular permeability ,Metastasis ,Transcriptome ,anti-angiogenic therapy ,Mice ,0302 clinical medicine ,Single-cell analysis ,Neoplasms ,Organisms::Eukaryota::Animals [Medical Subject Headings] ,Anatomy::Cells::Epithelial Cells::Endothelial Cells [Medical Subject Headings] ,Macrophage ,Myeloid Cells ,Biology (General) ,Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Mice::Mice, Inbred Strains::Mice, Inbred BALB C [Medical Subject Headings] ,Inbred BALB C ,Mice, Inbred BALB C ,Tumor ,cancer cells ,endothelial cells ,macrophages ,metastasis ,pericytes ,resistance ,single-cell RNA sequencing ,tumor angiogenesis ,tumor vessel co-option ,Animals ,Cell Line, Tumor ,Endothelial Cells ,Female ,Kidney Neoplasms ,Macrophages ,Pericytes ,Single-Cell Analysis ,Diseases::Neoplasms [Medical Subject Headings] ,3. Good health ,Metástasis de la neoplasia ,Pericitos ,Anatomy::Cells::Pericytes [Medical Subject Headings] ,Cell type ,QH301-705.5 ,Anatomy::Cells::Myeloid Cells [Medical Subject Headings] ,Biology ,Diseases::Neoplasms::Neoplasms by Site::Thoracic Neoplasms::Respiratory Tract Neoplasms::Lung Neoplasms [Medical Subject Headings] ,General Biochemistry, Genetics and Molecular Biology ,Cell Line ,03 medical and health sciences ,medicine ,Macrófagos ,Inductores de la angiogénesis ,Células endoteliales ,Cancer ,medicine.disease ,030104 developmental biology ,Cancer cell ,Cancer research ,Human medicine ,030217 neurology & neurosurgery - Abstract
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. ispartof: CELL REPORTS vol:35 issue:11 ispartof: location:United States status: published
- Published
- 2021