title: miR-155-deficient bone marrow promotes tumor metastasis.
abstract: Infiltration of immune cells in primary tumors and metastatic sites is known to influence tumor progression and metastasis. Macrophages represent the most abundant immune cells in the tumor microenvironment, and evidence has shown that macrophages promote seeding, extravasation, and persistent growth of tumor cells at metastatic sites. miR-155 plays an essential role in immune cell development/function, and its aberrant expression is associated with lymphomas and several solid tumor types. However, it is unknown how miR-155 expression in immune cells affects solid tumor growth and metastasis. To this end, bone marrow transplantation was performed using miR-155-deficient mice as bone marrow donors and wild-type (WT) mice as recipients, and the chimeric mice were inoculated with tumor cells. We demonstrate that bone marrow lacking miR-155 significantly enhanced lung metastasis without a substantial effect on primary tumor growth. Relative to mice with WT bone marrow, miR-155-deficient bone marrow accumulated more macrophages in the spleen and lungs. Further analysis revealed that miR-155-deficient macrophages in metastatic sites exhibited a tumor-promoting M2 phenotype. In vitro study suggested that miR-155-null macrophages were prone to M2 polarization upon incubation with tumor cell-conditioned medium, due to elevated expression of C/EBPβ, an identified miR-155 target. These data, for the first time, demonstrate that miR-155 in host immune cells plays a vital role in modulating solid tumor metastasis by affecting the recruitment and polarization of bone marrow-derived macrophages.
  
  
  CONCLUSIONS
  Targeted inhibition of miR-155 delays tumor development but inhibition in host immune cells may encourage metastasis.
authors.affiliation: Department of Cell Biology and Anatomy, University of South Carolina School of Medicine, 6439 Garners Ferry Road, Columbia, SC 29208, USA. yufang@fmmu.edu.cn
authors.forename: Fang
authors.initials: F
authors.lastname: Yu
authors.forename: Xuemei
authors.initials: X
authors.lastname: Jia
authors.forename: Fen
authors.initials: F
authors.lastname: Du
authors.forename: Junfeng
authors.initials: J
authors.lastname: Wang
authors.forename: Yuzhen
authors.initials: Y
authors.lastname: Wang
authors.forename: Walden
authors.initials: W
authors.lastname: Ai
authors.forename: Daping
authors.initials: D
authors.lastname: Fan
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism*; D016026:Bone Marrow Transplantation; D018827:Carcinoma, Lewis Lung / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D005260:Female; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology / Q000556:secondary*; D008264:Macrophages / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D009362:Neoplasm Metastasis; D059016:Tumor Microenvironment
chemical_list: D035683:MicroRNAs; C532623:Mirn155 microRNA, mouse