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S1PR1 on tumor-associated macrophages promotes lymphangiogenesis and metastasis via NLRP3/IL-1ß.
Weichand, Benjamin; Popp, Rüdiger; Dziumbla, Sarah; Mora, Javier; Strack, Elisabeth; Elwakeel, Eiman; Frank, Ann-Christin; Scholich, Klaus; Pierre, Sandra; Syed, Shahzad N; Olesch, Catherine; Ringleb, Julia; Ören, Bilge; Döring, Claudia; Savai, Rajkumar; Jung, Michaela; von Knethen, Andreas; Levkau, Bodo; Fleming, Ingrid; Weigert, Andreas; Brüne, Bernhard.
Afiliación
  • Weichand B; Institute of Biochemistry I, Faculty of Medicine, Goethe-University Frankfurt, Frankfurt, Germany.
  • Popp R; Institute of Vascular Signaling, Faculty of Medicine, Goethe-University Frankfurt, Frankfurt, Germany.
  • Dziumbla S; Institute of Vascular Signaling, Faculty of Medicine, Goethe-University Frankfurt, Frankfurt, Germany.
  • Mora J; Institute of Biochemistry I, Faculty of Medicine, Goethe-University Frankfurt, Frankfurt, Germany.
  • Strack E; Institute of Biochemistry I, Faculty of Medicine, Goethe-University Frankfurt, Frankfurt, Germany.
  • Elwakeel E; Institute of Biochemistry I, Faculty of Medicine, Goethe-University Frankfurt, Frankfurt, Germany.
  • Frank AC; Institute of Biochemistry I, Faculty of Medicine, Goethe-University Frankfurt, Frankfurt, Germany.
  • Scholich K; Institute of Clinical Pharmacology/Center for Drug Research, Development and Safety (ZAFES), Faculty of Medicine, Goethe-University Frankfurt, Frankfurt, Germany.
  • Pierre S; Institute of Clinical Pharmacology/Center for Drug Research, Development and Safety (ZAFES), Faculty of Medicine, Goethe-University Frankfurt, Frankfurt, Germany.
  • Syed SN; Institute of Biochemistry I, Faculty of Medicine, Goethe-University Frankfurt, Frankfurt, Germany.
  • Olesch C; Institute of Biochemistry I, Faculty of Medicine, Goethe-University Frankfurt, Frankfurt, Germany.
  • Ringleb J; Institute of Biochemistry I, Faculty of Medicine, Goethe-University Frankfurt, Frankfurt, Germany.
  • Ören B; Institute of Biochemistry I, Faculty of Medicine, Goethe-University Frankfurt, Frankfurt, Germany.
  • Döring C; Dr. Senckenberg Institute for Pathology, Goethe-University Frankfurt, Frankfurt, Germany.
  • Savai R; Max-Planck-Institute for Heart and Lung Research, Department of Lung Development and Remodeling, German Center for Lung Research (DZL), Bad Nauheim, Germany.
  • Jung M; Institute of Biochemistry I, Faculty of Medicine, Goethe-University Frankfurt, Frankfurt, Germany.
  • von Knethen A; Institute of Biochemistry I, Faculty of Medicine, Goethe-University Frankfurt, Frankfurt, Germany.
  • Levkau B; Institute of Pathophysiology, West German Heart and Vascular Center, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
  • Fleming I; Institute of Vascular Signaling, Faculty of Medicine, Goethe-University Frankfurt, Frankfurt, Germany.
  • Weigert A; Institute of Biochemistry I, Faculty of Medicine, Goethe-University Frankfurt, Frankfurt, Germany weigert@biochem.uni-frankfurt.de.
  • Brüne B; Institute of Biochemistry I, Faculty of Medicine, Goethe-University Frankfurt, Frankfurt, Germany b.bruene@biochem.uni-frankfurt.de.
J Exp Med ; 214(9): 2695-2713, 2017 Sep 04.
Article en En | MEDLINE | ID: mdl-28739604
Metastasis is the primary cause of cancer death. The inflammatory tumor microenvironment contributes to metastasis, for instance, by recruiting blood and lymph vessels. Among tumor-infiltrating immune cells, tumor-associated macrophages (TAMs) take a center stage in promoting both tumor angiogenesis and metastatic spread. We found that genetic deletion of the S1P receptor 1 (S1pr1) alone in CD11bhi CD206+ TAMs infiltrating mouse breast tumors prevents pulmonary metastasis and tumor lymphangiogenesis. Reduced lymphangiogenesis was also observed in the nonrelated methylcholanthrene-induced fibrosarcoma model. Transcriptome analysis of isolated TAMs from both entities revealed reduced expression of the inflammasome component Nlrp3 in S1PR1-deficient TAMs. Macrophage-dependent lymphangiogenesis in vitro was triggered upon inflammasome activation and required both S1PR1 signaling and IL-1ß production. Finally, NLRP3 expression in tumor-infiltrating macrophages correlated with survival, lymph node invasion, and metastasis of mammary carcinoma patients. Conceptually, our study indicates an unappreciated role of the NLRP3 inflammasome in promoting metastasis via the lymphatics downstream of S1PR1 signaling in macrophages.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Linfangiogénesis / Receptores de Lisoesfingolípidos / Interleucina-1beta / Proteína con Dominio Pirina 3 de la Familia NLR / Macrófagos / Metástasis de la Neoplasia Tipo de estudio: Risk_factors_studies Límite: Animals / Female / Humans Idioma: En Revista: J Exp Med Año: 2017 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Linfangiogénesis / Receptores de Lisoesfingolípidos / Interleucina-1beta / Proteína con Dominio Pirina 3 de la Familia NLR / Macrófagos / Metástasis de la Neoplasia Tipo de estudio: Risk_factors_studies Límite: Animals / Female / Humans Idioma: En Revista: J Exp Med Año: 2017 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Estados Unidos