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

Zhang, Huafeng; Yu, Yuandong; Zhou, Li; Ma, Jingwei; Tang, Ke; Xu, Pingwei; Ji, Tiantian; Liang, Xiaoyu; Lv, Jiadi; Dong, Wenqian; Zhang, Tianzhen; Chen, Degao; Xie, Jing; Liu, Yuying; Huang, Bo

doi:10.1158/2326-6066.22539919.v1

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

journal contribution

posted on 2023-04-03, 23:27 authored by Huafeng Zhang, Yuandong Yu, Li Zhou, Jingwei Ma, Ke Tang, Pingwei Xu, Tiantian Ji, Xiaoyu Liang, Jiadi Lv, Wenqian Dong, Tianzhen Zhang, Degao Chen, Jing Xie, Yuying Liu, Bo Huang

Supplementary Figure S1. Size distribution of T-MPs isolated from hypoxic or normoxic tumor cells. Supplementary Figure S2. Analysis of lung metastasis and overall survival after tail vein injection of 4T1 breast cancer cells in mice pretreated with 4T1-MPï¼ŒS-MP or PBS. Supplementary Figure S3. Confocal microscopic analysis of PKH26-MPs in lung. Supplementary Figure S4. Analysis of lung endothelial permeability. Supplementary Figure S5. The proportion of T cells, B cells and NK cells in the lungs were analyzed by flow cytometry after treatment of with 4T1-MPï¼ŒS-MP or PBS. Supplementary Figure S6. CCL2 was mainly produced by lung macrophages that had taken up T-MPs. Figure S7. DNA fragments in hypoxic tumor cell-MPs contribute to macrophages upregulating CCL2 expression via the cGAS/STING/STAT6 pathway. Supplementary Figure S8. CCL2-attracted monocytes transit to macrophages. Supplementary Figure S9. F4/80+CD11b+Ly6C- macrophages effectively inhibited OVA257-264 peptide-stimulated OT-1 T cell proliferation in vitro and in vivo. Supplementary Figure S10. T-MP-induced VEGF production by macrophages contributes fibrin deposition in the lungs.

Funding

National Natural Science Foundation of China

History

ARTICLE 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.