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.

Unique Features of Ethnic Mongolian Gut Microbiome revealed by metagenomic analysis

“…The increased pathway abundance of carbohydrate, amino acid and nucleotide sugar, and phosphotransferase and aminoacyl-tRNA of intestinal microbiota in Mongolians suggested the more vigorous microbial growth and metabolic stage in Mongolian’s gut compared with that of Han Chinese. The aminoacyl-tRNA was able to combine with its corresponding animal acid, and transferred the animal acid to the ribosome 26 . In present research, we found the biosynthesis of aminoacyl-tRNA was enhanced which indicated an overall enhanced level of microbial gene expression in the gut of Mongolians.…”

AIMp1 Potentiates TH1 Polarization and Is Critical for Effective Antitumor and Antiviral Immunity

“…Antitumor immunity is broadly dependent upon T H 1 immune processes for destruction of neoplastic cells ( 34 – 36 ), and immunity to B16 melanoma is specifically known to be dependent upon T H 1 T-cell generation ( 37 ). Administration of recombinant E. coli -expressed human AIMp1 protein to tumor-bearing mice has been shown to have tumor inhibitory effects in a human xenograft model of stomach cancer ( 38 , 39 ) as well as EG7 lymphoma ( 40 ), breast cancer ( 41 ), and others. To determine if intrinsic AIMp1 might possess inherent antitumor properties under conditions of physiologic homeostasis, we inoculated AIMp1 −/− mice with B16F10 melanoma and observed a tumor growth rate nearly double that exhibited in WT animals (Figure 1 A).…”

Dual functional bioactive‐peptide,AIMP1‐derived peptide (AdP), for anti‐aging

“…When it was discovered, it was identified as a cofactor protein that provides an efficient aminoacyl-tRNA synthesis trafficking channel for translation. 20 Moreover, the level of AIMP1 is increased in wounded skin, and AIMP1 plays a significant role in wound healing, 17 an AIMP1-derived peptide (AdP, amino acid region 6-46, sh-oligopeptide 5/sh-oligoepeptide 5 SP) has the potential to be used as a cosmeceutical. AdP showed more potent activity for promoting fibroblast proliferation and collagen type I synthesis than EGF, a representative cosmeceutical ingredient.…”

“…AIMP1 is associated with the multi‐aminoacyl‐tRNA synthetase complex. When it was discovered, it was identified as a cofactor protein that provides an efficient aminoacyl‐tRNA synthesis trafficking channel for translation . Moreover, the level of AIMP1 is increased in wounded skin, and AIMP1 plays a significant role in wound healing, an AIMP1‐derived peptide (AdP, amino acid region 6‐46, sh‐oligopeptide 5/sh‐oligoepeptide 5 SP) has the potential to be used as a cosmeceutical.…”