Tissue-resident macrophages in omentum promote metastatic spread of ovarian cancer

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DOI

  • Anders Etzerodt
  • Morgane Moulin, Aix Marseille Univ, CNRS, INSERM, CIML, Marseille, France., King’s College London
  • ,
  • Thomas Koed Doktor, University of Southern Denmark
  • ,
  • Marcello Delfini, Aix Marseille Univ, CNRS, INSERM, CIML, Marseille, France.
  • ,
  • Noushine Mossadegh-Keller, Aix Marseille Univ, CNRS, INSERM, CIML, Marseille, France.
  • ,
  • Marc Bajenoff, Aix Marseille Univ, CNRS, INSERM, CIML, Marseille, France.
  • ,
  • Michael H Sieweke, TU Dresden, Aix Marseille Univ, CNRS, INSERM, CIML, Marseille, France.
  • ,
  • Søren Kragh Moestrup
  • Nathalie Auphan-Anezin, Aix Marseille Univ, CNRS, INSERM, CIML, Marseille, France.
  • ,
  • Toby Lawrence, Aix Marseille Univ, CNRS, INSERM, CIML, Marseille, France., King’s College London, Xinxiang University

Experimental and clinical evidence suggests that tumor-associated macrophages (TAMs) play important roles in cancer progression. Here, we have characterized the ontogeny and function of TAM subsets in a mouse model of metastatic ovarian cancer that is representative for visceral peritoneal metastasis. We show that the omentum is a critical premetastatic niche for development of invasive disease in this model and define a unique subset of CD163+ Tim4+ resident omental macrophages responsible for metastatic spread of ovarian cancer cells. Transcriptomic analysis showed that resident CD163+ Tim4+ omental macrophages were phenotypically distinct and maintained their resident identity during tumor growth. Selective depletion of CD163+ Tim4+ macrophages in omentum using genetic and pharmacological tools prevented tumor progression and metastatic spread of disease. These studies describe a specific role for tissue-resident macrophages in the invasive progression of metastatic ovarian cancer. The molecular pathways of cross-talk between tissue-resident macrophages and disseminated cancer cells may represent new targets to prevent metastasis and disease recurrence.

Original languageEnglish
Article numbere20191869
JournalThe Journal of Experimental Medicine
Volume217
Issue4
ISSN0022-1007
DOIs
Publication statusPublished - Apr 2020

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