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
PY - 2020/4/6
Y1 - 2020/4/6
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.
UR - http://www.scopus.com/inward/record.url?scp=85077941778&partnerID=8YFLogxK
U2 - 10.1084/jem.20191869
DO - 10.1084/jem.20191869
M3 - 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 -
