N. Linde, M. Casanova-Acebes, M. Sosa, A. Mortha, Adeeb H. Rahman, E. Farias, K. Harper, E. Tardio, Iván Reyes-Torres, Joan G. Jones, J. Condeelis, M. Merad, J. Aguirre-Ghiso
{"title":"Abstract IA16: Macrophages orchestrate early dissemination and metastasis","authors":"N. Linde, M. Casanova-Acebes, M. Sosa, A. Mortha, Adeeb H. Rahman, E. Farias, K. Harper, E. Tardio, Iván Reyes-Torres, Joan G. Jones, J. Condeelis, M. Merad, J. Aguirre-Ghiso","doi":"10.1158/2326-6074.TUMIMM17-IA16","DOIUrl":"https://doi.org/10.1158/2326-6074.TUMIMM17-IA16","url":null,"abstract":"Cancer cell dissemination can occur during very early stages of breast cancer, but the mechanisms controlling this process are unclear. Here we show that a previously reported early MMTV-HER2+/P-p38lo/TWISThi/E-cadherinlo cancer cell subpopulation depends on macrophages for early dissemination. Depletion of macrophages before overt tumor detection drastically reduced early dissemination and diminished the late metastatic burden. CD206+/Tie2+ macrophages were attracted into early lesions in part by CCL2 produced by early HER2+ cancer cells and myeloid cells. Upregulation of Wnt-1 by macrophages could be stimulated by CCL2 and correlated with loss of E-cadherin in HER2+ early cancer cells. Both MMTV-PyMT and MMTV-HER2 early lesions showed macrophage-containing tumor microenvironments of metastasis (TMEM) structures, and PyMT early cancer cells also showed a reduction in early lesion E-cadherin junctions. Intraepithelial macrophages and loss of E-cadherin junctions was also found more frequently in high-grade human DCIS than in low-grade and normal breast tissue, but no association was found with HER2 status. We reveal a previously unrecognized mechanism by which macrophages play a causal role in early dissemination, impacting long-term metastasis development. Citation Format: Nina Linde, Maria Casanova-Acebes, Maria Soledad Sosa, Arthur Mortha, Adeeb Rahman, Eduardo F. Farias, Kathryn Harper, Ethan Tardio, Ivan Reyes-Torres, Joan G. Jones, John S. Condeelis, Miriam Merad, Julio A. Aguirre-Ghiso. Macrophages orchestrate early dissemination and metastasis [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2017 Oct 1-4; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2018;6(9 Suppl):Abstract nr IA16.","PeriodicalId":144128,"journal":{"name":"The Inflammatory Tumor Microenvironment","volume":"5 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2018-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"125983006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}