Tissue-resident macrophages in omentum promote metastatic spread of ovarian cancer
Research output: Contribution to journal › Research article › Contributed › peer-review
Contributors
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.
Details
Original language | English |
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Article number | e20191869 |
Journal | The Journal of experimental medicine |
Volume | 217 |
Issue number | 4 |
Publication status | Published - 6 Apr 2020 |
Peer-reviewed | Yes |
External IDs
PubMedCentral | PMC7144521 |
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Scopus | 85077941778 |
Keywords
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