Circulating Tumor Microparticles Promote Lung Metastasis by Reprogramming Inflammatory and Mechanical Niches via a Macrophage-Dependent Pathway

Cancer Immunology Research
Huafeng ZhangBo Huang

Abstract

Despite the frequency of lung metastasis and its associated mortality, the mechanisms behind metastatic tumor cell survival and colonization in the lungs remain elusive. Here, we show that tumor cell-released microparticles (T-MPs) from the primary tumor site play a critical role in the metastatic process. The T-MPs remodeled the lung parenchyma via a macrophage-dependent pathway to create an altered inflammatory and mechanical response to tumor cell invasion. Mechanistically, we show that circulating T-MPs readily enter the lung parenchyma where they are taken up by local macrophages and induce CCL2 production. CCL2 recruits CD11b+Ly6Chigh inflammatory monocytes to the lungs where they mature into F4/80+CD11b+Ly6C- macrophages that not only produce IL6 but also trigger fibrin deposition. IL6 and the deposited fibrin facilitate the survival and growth of tumor-repopulating cells in the lungs by providing chemical and mechanical signals, respectively, thus setting the stage for lung metastasis. These data illustrate that T-MPs reprogram the lung microenvironment promoting metastasis. Cancer Immunol Res; 6(9); 1046-56. ©2018 AACR.

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Citations

Jun 2, 2020·Chemical Communications : Chem Comm·Zhijie ZhangZifu Li
Jan 2, 2019·Nature Cell Biology·Ioanna KeklikoglouMichele De Palma
Jan 2, 2019·International Journal of Molecular Sciences·Naofumi MukaidaTomohisa Baba
Aug 27, 2019·Frontiers in Immunology·Stefania CanèVincenzo Bronte
Jan 4, 2020·Cancer Immunology, Immunotherapy : CII·Pazit SalamonIrit Shefler
Jun 2, 2020·Frontiers in Immunology·Ioana IurcaIoana Berindan-Neagoe
Sep 26, 2020·European Journal of Immunology·Jingwei MaBo Huang
Feb 5, 2021·Frontiers in Oncology·Yalin KangXianglin Yuan
Feb 13, 2021·Molecular Therapy. Methods & Clinical Development·Margaret L DahnPaola Marcato
Jun 9, 2021·Current Protocols·Jingwei MaBo Huang

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