title: Aminoacyl-tRNA synthetase-interacting multifunctional protein 1 suppresses tumor growth in breast cancer-bearing mice by negatively regulating myeloid-derived suppressor cell functions.
abstract: Myeloid-derived suppressor cells (MDSCs) are one of the most important cell types that contribute to negative regulation of immune responses in the tumor microenvironment. Recently, aminoacyl-tRNA synthetase-interacting multifunctional protein 1 (AIMP1), a novel pleiotropic cytokine, was identified as an antitumor protein that inhibits angiogenesis and induces antitumor responses. However, the effect of AIMP1 on MDSCs in the tumor environment remains unclear. In the present study, we demonstrated that AIMP1 significantly inhibited tumor growth in 4T1 breast cancer-bearing mice and reduced MDSCs population of tumor sites and spleens of tumor-bearing mice. AIMP1 reduced expansion of MDSCs from bone marrow-derived cells in the tumor-conditioned media. AIMP1 also negatively regulated suppressive activities of MDSCs by inhibiting IL-6 and NO production, and Arg-1 expression. Furthermore, treatment of breast cancer-bearing mice with AIMP1 decreased the capacity of MDSCs to suppress T cell proliferation and Treg cell induction. Western blot and inhibition experiments showed that downregulation of MDSCs functions by AIMP1 may result from attenuated activation of STATs, Akt, and ERK. These findings indicate that AIMP1 plays an essential role in negative regulation of suppressive functions of MDSCs. Therefore, it has a significant potential as a therapeutic agent for cancer treatment.
authors.affiliation: Division of Life Sciences, College of Life Sciences and Biotechnology, Korea University, Room 607, Hana Science Building, Anam-dong 5-ga, Seongbuk-gu, Seoul, 136-701, Republic of Korea.
authors.forename: Hye-Jin
authors.initials: HJ
authors.lastname: Hong
authors.affiliation: Division of Life Sciences, College of Life Sciences and Biotechnology, Korea University, Room 607, Hana Science Building, Anam-dong 5-ga, Seongbuk-gu, Seoul, 136-701, Republic of Korea.
authors.forename: Hui Xuan
authors.initials: HX
authors.lastname: Lim
authors.affiliation: Division of Life Sciences, College of Life Sciences and Biotechnology, Korea University, Room 607, Hana Science Building, Anam-dong 5-ga, Seongbuk-gu, Seoul, 136-701, Republic of Korea.
authors.forename: Ju Han
authors.initials: JH
authors.lastname: Song
authors.affiliation: Division of Life Sciences, College of Life Sciences and Biotechnology, Korea University, Room 607, Hana Science Building, Anam-dong 5-ga, Seongbuk-gu, Seoul, 136-701, Republic of Korea.
authors.forename: Arim
authors.initials: A
authors.lastname: Lee
authors.affiliation: Division of Life Sciences, College of Life Sciences and Biotechnology, Korea University, Room 607, Hana Science Building, Anam-dong 5-ga, Seongbuk-gu, Seoul, 136-701, Republic of Korea.
authors.forename: Eugene
authors.initials: E
authors.lastname: Kim
authors.affiliation: Division of Life Science, Sookmyung Women's University, Seoul, 140-742, Republic of Korea.
authors.forename: Daeho
authors.initials: D
authors.lastname: Cho
authors.affiliation: Department of Microbiology and Immunology, University of Illinois College of Medicine, Chicago, IL, 60612, USA.
authors.forename: Edward P
authors.initials: EP
authors.lastname: Cohen
authors.affiliation: Division of Life Sciences, College of Life Sciences and Biotechnology, Korea University, Room 607, Hana Science Building, Anam-dong 5-ga, Seongbuk-gu, Seoul, 136-701, Republic of Korea. tskim@korea.ac.kr.
authors.forename: Tae Sung
authors.initials: TS
authors.lastname: Kim
mesh_terms: D000604:Amino Acyl-tRNA Synthetases / Q000276:immunology*; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D001943:Breast Neoplasms / Q000276:immunology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D022423:Myeloid Cells / Q000276:immunology*
chemical_list: D000604:Amino Acyl-tRNA Synthetases
keywords: AIMP1; Breast cancer; Mice; Myeloid-derived suppressor cells; T cells