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

Anders Etzerodt, Morgane Moulin, Thomas Koed Doktor, Marcello Delfini, Noushine Mossadegh-Keller, Marc Bajenoff, Michael H Sieweke, Søren Kragh Moestrup, Nathalie Auphan-Anezin, Toby Lawrence

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

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Abstract

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

Keywords

  • Animals
  • Antigens, CD/genetics
  • Antigens, Differentiation, Myelomonocytic/genetics
  • Disease Models, Animal
  • Disease Progression
  • Female
  • Gene Expression Profiling
  • Macrophages/metabolism
  • Membrane Proteins/metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Omentum/metabolism
  • Ovarian Neoplasms/metabolism
  • Peritoneal Neoplasms/metabolism
  • Phenotype
  • Receptors, Cell Surface/genetics
  • Transcriptome

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