Single cell atlas identifies lipid-processing and immunomodulatory endothelial cells in healthy and malignant breast.

Autor: Geldhof V; Laboratory of Angiogenesis and Vascular Metabolism, Center for Cancer Biology (CCB), VIB, Department of Oncology, Leuven Cancer Institute (LKI), KU Leuven, Leuven, 3000, Belgium., de Rooij LPMH; Laboratory of Angiogenesis and Vascular Metabolism, Center for Cancer Biology (CCB), VIB, Department of Oncology, Leuven Cancer Institute (LKI), KU Leuven, Leuven, 3000, Belgium., Sokol L; Laboratory of Angiogenesis and Vascular Metabolism, Center for Cancer Biology (CCB), VIB, Department of Oncology, Leuven Cancer Institute (LKI), KU Leuven, Leuven, 3000, Belgium., Amersfoort J; Laboratory of Angiogenesis and Vascular Metabolism, Center for Cancer Biology (CCB), VIB, Department of Oncology, Leuven Cancer Institute (LKI), KU Leuven, Leuven, 3000, Belgium., De Schepper M; Laboratory for Translational Breast Cancer Research, Department of Oncology, KU Leuven, Leuven, Belgium.; Department of Pathology, University Hospitals Leuven, Leuven, Belgium., Rohlenova K; Laboratory of Angiogenesis and Vascular Metabolism, Center for Cancer Biology (CCB), VIB, Department of Oncology, Leuven Cancer Institute (LKI), KU Leuven, Leuven, 3000, Belgium.; Institute of Biotechnology of the Czech Academy of Sciences, BIOCEV, Vestec, Prague-West, Czech Republic., Hoste G; Department of General Medical Oncology and Multidisciplinary Breast Centre, University Hospitals Leuven, Leuven, Belgium.; Department of Gynaecologic Oncology, Leuven Cancer Institute, University Hospital Leuven, KU Leuven, Leuven, Belgium., Vanderstichele A; Department of General Medical Oncology and Multidisciplinary Breast Centre, University Hospitals Leuven, Leuven, Belgium.; Department of Gynaecologic Oncology, Leuven Cancer Institute, University Hospital Leuven, KU Leuven, Leuven, Belgium., Delsupehe AM; Department of Pathology, University Hospitals Leuven, Leuven, Belgium., Isnaldi E; Laboratory for Translational Breast Cancer Research, Department of Oncology, KU Leuven, Leuven, Belgium., Dai N; Laboratory of Angiogenesis and Vascular Metabolism, Center for Cancer Biology (CCB), VIB, Department of Oncology, Leuven Cancer Institute (LKI), KU Leuven, Leuven, 3000, Belgium., Taverna F; Laboratory of Angiogenesis and Vascular Metabolism, Center for Cancer Biology (CCB), VIB, Department of Oncology, Leuven Cancer Institute (LKI), KU Leuven, Leuven, 3000, Belgium., Khan S; Laboratory of Angiogenesis and Vascular Metabolism, Center for Cancer Biology (CCB), VIB, Department of Oncology, Leuven Cancer Institute (LKI), KU Leuven, Leuven, 3000, Belgium.; National Center for Cancer Immune Therapy, Department of Oncology, University of Copenhagen, Herlev, Denmark., Truong AK; Laboratory of Angiogenesis and Vascular Metabolism, Center for Cancer Biology (CCB), VIB, Department of Oncology, Leuven Cancer Institute (LKI), KU Leuven, Leuven, 3000, Belgium., Teuwen LA; Laboratory of Angiogenesis and Vascular Metabolism, Center for Cancer Biology (CCB), VIB, Department of Oncology, Leuven Cancer Institute (LKI), KU Leuven, Leuven, 3000, Belgium.; Translational Cancer Research Unit, GZA Hospitals Sint-Augustinus, Antwerp, Belgium and Center for Oncological Research, University of Antwerp, Antwerp, Belgium., Richard F; Laboratory for Translational Breast Cancer Research, Department of Oncology, KU Leuven, Leuven, Belgium., Treps L; Laboratory of Angiogenesis and Vascular Metabolism, Center for Cancer Biology (CCB), VIB, Department of Oncology, Leuven Cancer Institute (LKI), KU Leuven, Leuven, 3000, Belgium., Smeets A; Multidisciplinary Breast Centre and Department of Surgical Oncology, University Hospitals Leuven, KU Leuven, Leuven, Belgium., Nevelsteen I; Multidisciplinary Breast Centre and Department of Surgical Oncology, University Hospitals Leuven, KU Leuven, Leuven, Belgium., Weynand B; Department of Pathology, University Hospitals Leuven, Leuven, Belgium.; Laboratory of Translational Cell & Tissue Research, Department of Imaging and Pathology, KU Leuven, Leuven, 3000, Belgium., Vinckier S; Laboratory of Angiogenesis and Vascular Metabolism, Center for Cancer Biology (CCB), VIB, Department of Oncology, Leuven Cancer Institute (LKI), KU Leuven, Leuven, 3000, Belgium., Schoonjans L; Laboratory of Angiogenesis and Vascular Metabolism, Center for Cancer Biology (CCB), VIB, Department of Oncology, Leuven Cancer Institute (LKI), KU Leuven, Leuven, 3000, Belgium.; State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, 510275, Guangzhou, Guangdong, People's Republic of China., Kalucka J; Aarhus University of Advanced Studies (AIAS), Aarhus University, Aarhus, 8000, Denmark.; Department of Biomedicine, Aarhus University, Aarhus, 8000, Denmark.; Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, 8000, Denmark., Desmedt C; Laboratory for Translational Breast Cancer Research, Department of Oncology, KU Leuven, Leuven, Belgium., Neven P; Department of General Medical Oncology and Multidisciplinary Breast Centre, University Hospitals Leuven, Leuven, Belgium.; Department of Gynaecologic Oncology, Leuven Cancer Institute, University Hospital Leuven, KU Leuven, Leuven, Belgium., Mazzone M; Laboratory of Tumor Inflammation and Angiogenesis, Center for Cancer Biology, Department of oncology, KU Leuven, Leuven, 3000, Belgium.; Laboratory of Tumor Inflammation and Angiogenesis, Center for Cancer Biology, VIB, Leuven, 3000, Belgium., Floris G; Department of Pathology, University Hospitals Leuven, Leuven, Belgium.; Department of General Medical Oncology and Multidisciplinary Breast Centre, University Hospitals Leuven, Leuven, Belgium.; Laboratory of Translational Cell & Tissue Research, Department of Imaging and Pathology, KU Leuven, Leuven, 3000, Belgium., Punie K; Department of General Medical Oncology and Multidisciplinary Breast Centre, University Hospitals Leuven, Leuven, Belgium., Dewerchin M; Laboratory of Angiogenesis and Vascular Metabolism, Center for Cancer Biology (CCB), VIB, Department of Oncology, Leuven Cancer Institute (LKI), KU Leuven, Leuven, 3000, Belgium., Eelen G; Laboratory of Angiogenesis and Vascular Metabolism, Center for Cancer Biology (CCB), VIB, Department of Oncology, Leuven Cancer Institute (LKI), KU Leuven, Leuven, 3000, Belgium., Wildiers H; Department of General Medical Oncology and Multidisciplinary Breast Centre, University Hospitals Leuven, Leuven, Belgium., Li X; State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, 510275, Guangzhou, Guangdong, People's Republic of China. lixr6@mail.sysu.edu.cn., Luo Y; Department of Biomedicine, Aarhus University, Aarhus, 8000, Denmark. alun@biomed.au.dk.; Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, 8000, Denmark. alun@biomed.au.dk.; Lars Bolund Institute of Regenerative Medicine, Qingdao-Europe Advanced Institute for Life Sciences, BGI-Shenzhen, Qingdao, 266555, China. alun@biomed.au.dk., Carmeliet P; Laboratory of Angiogenesis and Vascular Metabolism, Center for Cancer Biology (CCB), VIB, Department of Oncology, Leuven Cancer Institute (LKI), KU Leuven, Leuven, 3000, Belgium. peter.carmeliet@kuleuven.be.; State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, 510275, Guangzhou, Guangdong, People's Republic of China. peter.carmeliet@kuleuven.be.; Laboratory of Angiogenesis and Vascular Heterogeneity, Department of Biomedicine, Aarhus University, Aarhus, 8000, Denmark. peter.carmeliet@kuleuven.be.; Center for Biotechnology, Khalifa University of Science and Technology, Abu Dhabi, United Arab Emirates. peter.carmeliet@kuleuven.be.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2022 Sep 20; Vol. 13 (1), pp. 5511. Date of Electronic Publication: 2022 Sep 20.
DOI: 10.1038/s41467-022-33052-y
Abstrakt: Since a detailed inventory of endothelial cell (EC) heterogeneity in breast cancer (BC) is lacking, here we perform single cell RNA-sequencing of 26,515 cells (including 8433 ECs) from 9 BC patients and compare them to published EC taxonomies from lung tumors. Angiogenic ECs are phenotypically similar, while other EC subtypes are different. Predictive interactome analysis reveals known but also previously unreported receptor-ligand interactions between ECs and immune cells, suggesting an involvement of breast EC subtypes in immune responses. We also identify a capillary EC subtype (LIPEC (Lipid Processing EC)), which expresses genes involved in lipid processing that are regulated by PPAR-γ and is more abundant in peri-tumoral breast tissue. Retrospective analysis of 4648 BC patients reveals that treatment with metformin (an indirect PPAR-γ signaling activator) provides long-lasting clinical benefit and is positively associated with LIPEC abundance. Our findings warrant further exploration of this LIPEC/PPAR-γ link for BC treatment.
(© 2022. The Author(s).)
Databáze: MEDLINE
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