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Endothelial Notch1 signaling in white adipose tissue promotes cancer cachexia.
Taylor, Jacqueline; Uhl, Leonie; Moll, Iris; Hasan, Sana Safatul; Wiedmann, Lena; Morgenstern, Jakob; Giaimo, Benedetto Daniele; Friedrich, Tobias; Alsina-Sanchis, Elisenda; De Angelis Rigotti, Francesca; Mülfarth, Ronja; Kaltenbach, Sarah; Schenk, Darius; Nickel, Felix; Fleming, Thomas; Sprinzak, David; Mogler, Carolin; Korff, Thomas; Billeter, Adrian T; Müller-Stich, Beat P; Berriel Diaz, Mauricio; Borggrefe, Tilman; Herzig, Stephan; Rohm, Maria; Rodriguez-Vita, Juan; Fischer, Andreas.
Afiliación
  • Taylor J; Division Vascular Signaling and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Uhl L; Division Vascular Signaling and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Moll I; Theodor Boveri Institute, Department of Biochemistry and Molecular Biology, Biocenter, University of Würzburg, Würzburg, Germany.
  • Hasan SS; Division Vascular Signaling and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Wiedmann L; Division Vascular Signaling and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Morgenstern J; Department of Clinical Chemistry, University Medical Center Göttingen, Göttingen, Germany.
  • Giaimo BD; Division Vascular Signaling and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Friedrich T; Department of Internal Medicine Endocrinology and Clinical Chemistry, University of Heidelberg, Heidelberg, Germany.
  • Alsina-Sanchis E; Institute of Biochemistry, University of Giessen, Giessen, Germany.
  • De Angelis Rigotti F; Institute of Biochemistry, University of Giessen, Giessen, Germany.
  • Mülfarth R; Biomedical Informatics and Systems Medicine, Science Unit for Basic and Clinical Medicine, Giessen, Germany.
  • Kaltenbach S; Division Vascular Signaling and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Schenk D; Department of Clinical Chemistry, University Medical Center Göttingen, Göttingen, Germany.
  • Nickel F; Division Vascular Signaling and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Fleming T; Tumor-Stroma Communication Laboratory, Centro de Investigación Príncipe Felipe, Valencia, Spain.
  • Sprinzak D; Division Vascular Signaling and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Mogler C; Department of Clinical Chemistry, University Medical Center Göttingen, Göttingen, Germany.
  • Korff T; Division Vascular Signaling and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Billeter AT; Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany.
  • Müller-Stich BP; Department of Internal Medicine Endocrinology and Clinical Chemistry, University of Heidelberg, Heidelberg, Germany.
  • Berriel Diaz M; German Center of Diabetes Research (DZD), Neuherberg, Germany.
  • Borggrefe T; School of Neurobiology, Biochemistry and Biophysics, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.
  • Herzig S; Institute of Pathology, Technical University of Munich School of Medicine, Technical University of Munich, Munich, Germany.
  • Rohm M; Institute of Physiology and Pathophysiology, Department of Cardiovascular Physiology, University of Heidelberg, Heidelberg, Germany.
  • Rodriguez-Vita J; European Center for Angioscience (ECAS), Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
  • Fischer A; Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany.
Nat Cancer ; 4(11): 1544-1560, 2023 Nov.
Article en En | MEDLINE | ID: mdl-37749321
Cachexia is a major cause of morbidity and mortality in individuals with cancer and is characterized by weight loss due to adipose and muscle tissue wasting. Hallmarks of white adipose tissue (WAT) remodeling, which often precedes weight loss, are impaired lipid storage, inflammation and eventually fibrosis. Tissue wasting occurs in response to tumor-secreted factors. Considering that the continuous endothelium in WAT is the first line of contact with circulating factors, we postulated whether the endothelium itself may orchestrate tissue remodeling. Here, we show using human and mouse cancer models that during precachexia, tumors overactivate Notch1 signaling in distant WAT endothelium. Sustained endothelial Notch1 signaling induces a WAT wasting phenotype in male mice through excessive retinoic acid production. Pharmacological blockade of retinoic acid signaling was sufficient to inhibit WAT wasting in a mouse cancer cachexia model. This demonstrates that cancer manipulates the endothelium at distant sites to mediate WAT wasting by altering angiocrine signals.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Caquexia / Receptor Notch1 / Tejido Adiposo Blanco / Neoplasias Tipo de estudio: Prognostic_studies Límite: Animals / Humans / Male Idioma: En Revista: Nat Cancer Año: 2023 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Caquexia / Receptor Notch1 / Tejido Adiposo Blanco / Neoplasias Tipo de estudio: Prognostic_studies Límite: Animals / Humans / Male Idioma: En Revista: Nat Cancer Año: 2023 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Reino Unido