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

TY - JOUR

T1 - Tissue-resident macrophages in omentum promote metastatic spread of ovarian cancer

AU - Etzerodt, Anders

AU - Moulin, Morgane

AU - Doktor, Thomas Koed

AU - Delfini, Marcello

AU - Mossadegh-Keller, Noushine

AU - Bajenoff, Marc

AU - Sieweke, Michael H

AU - Moestrup, Søren Kragh

AU - Auphan-Anezin, Nathalie

AU - Lawrence, Toby

N1 - © 2020 Etzerodt et al.

PY - 2020/4

Y1 - 2020/4

N2 - 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.

AB - 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.

KW - Animals

KW - Antigens, CD/genetics

KW - Antigens, Differentiation, Myelomonocytic/genetics

KW - Disease Models, Animal

KW - Disease Progression

KW - Female

KW - Gene Expression Profiling

KW - Macrophages/metabolism

KW - Membrane Proteins/metabolism

KW - Mice

KW - Mice, Inbred C57BL

KW - Mice, Transgenic

KW - Omentum/metabolism

KW - Ovarian Neoplasms/metabolism

KW - Peritoneal Neoplasms/metabolism

KW - Phenotype

KW - Receptors, Cell Surface/genetics

KW - Transcriptome

U2 - 10.1084/jem.20191869

DO - 10.1084/jem.20191869

M3 - Journal article

C2 - 31951251

SN - 0022-1007

VL - 217

JO - The Journal of Experimental Medicine

JF - The Journal of Experimental Medicine

IS - 4

M1 - e20191869

ER -