title: Zfra activates memory Hyal-2+ CD3- CD19- spleen cells to block cancer growth, stemness, and metastasis in vivo.
abstract: Zfra is a 31-amino-acid zinc finger-like protein, which participates in the tumor necrosis factor signaling. Here, we determined that when nude mice and BALB/c mice were pre-injected with nanogram levels of a synthetic Zfra1-31 or truncated Zfra4-10 peptide via tail veins, these mice became resistant to the growth, metastasis and stemness of melanoma cells, and many malignant cancer cells. The synthetic peptides underwent self-polymerization in phosphate-buffered saline. Alteration of the Ser8 phosphorylation site to Gly8 abolished Zfra aggregation and its-mediated cancer suppression in vivo. Injected Zfra peptide autofluoresced due to polymerization and was trapped mainly in the spleen. Transfer of Zfra-stimulated spleen cells to naïve mice conferred resistance to cancer growth. Zfra-binding cells, designated Hyal-2+ CD3- CD19- Z cells, are approximately 25-30% in the normal spleen, but are significantly downregulated (near 0-3%) in tumor-growing mice. Zfra prevented the loss of Z cells caused by tumors. In vitro stimulation or education of naïve spleen cells with Zfra allowed generation of activated Z cells to confer a memory anticancer response in naïve or cancer-growing mice. In particular, Z cells are abundant in nude and NOD-SCID mice, and can be readily activated by Zfra to mount against cancer growth.
authors: Institute of Molecular Medicine, National Cheng Kung University Medical College, Tainan, Taiwan, ROC.
authors: Ming-Hui
authors: MH
authors: Lee
authors: Institute of Molecular Medicine, National Cheng Kung University Medical College, Tainan, Taiwan, ROC.
authors: Wan-Pei
authors: WP
authors: Su
authors: Institute of Molecular Medicine, National Cheng Kung University Medical College, Tainan, Taiwan, ROC.
authors: Wan-Jen
authors: WJ
authors: Wang
authors: Institute of Molecular Medicine, National Cheng Kung University Medical College, Tainan, Taiwan, ROC.
authors: Sing-Ru
authors: SR
authors: Lin
authors: Institute of Molecular Medicine, National Cheng Kung University Medical College, Tainan, Taiwan, ROC.
authors: Chen-Yu
authors: CY
authors: Lu
authors: Institute of Molecular Medicine, National Cheng Kung University Medical College, Tainan, Taiwan, ROC.
authors: Yu-An
authors: YA
authors: Chen
authors: Institute of Molecular Medicine, National Cheng Kung University Medical College, Tainan, Taiwan, ROC.
authors: Jean-Yun
authors: JY
authors: Chang
authors: Institute of Molecular Medicine, National Cheng Kung University Medical College, Tainan, Taiwan, ROC.
authors: Shenq-Shyang
authors: SS
authors: Huang
authors: Institute of Molecular Medicine, National Cheng Kung University Medical College, Tainan, Taiwan, ROC.
authors: Pei-Yi
authors: PY
authors: Chou
authors: Institute of Molecular Medicine, National Cheng Kung University Medical College, Tainan, Taiwan, ROC.
authors: Siou-Ru
authors: SR
authors: Ye
authors: Institute of Molecular Medicine, National Cheng Kung University Medical College, Tainan, Taiwan, ROC.
authors: Szu-Jung
authors: SJ
authors: Chen
authors: Institute of Molecular Medicine, National Cheng Kung University Medical College, Tainan, Taiwan, ROC.
authors: Huan
authors: H
authors: He
authors: Institute of Molecular Medicine, National Cheng Kung University Medical College, Tainan, Taiwan, ROC.
authors: Ting-Hsiu
authors: TH
authors: Liu
authors: Institute of Basic Medical Sciences, National Cheng Kung University Medical College, Tainan, Taiwan, ROC.
authors: Ying-Tsen
authors: YT
authors: Chou
authors: Department of Medical Laboratory Science and Biotechnology, National Cheng Kung University Medical College, Tainan, Taiwan, ROC.|Center of Infectious Disease and Signal Research, National Cheng Kung University, Tainan, Taiwan, ROC.
authors: Li-Jin
authors: LJ
authors: Hsu
authors: Department of Dermatology, Chi-Mei Medical Center, Tainan, Taiwan, ROC.
authors: Feng-Jie
authors: FJ
authors: Lai
authors: Advanced Optoelectronic Technology Center, National Cheng Kung University Medical College, Tainan, Taiwan, ROC.
authors: Shean-Jen
authors: SJ
authors: Chen
authors: Graduate Institute of Systems Biology and Bioinformatics, National Central University, Zhongli, Taiwan, ROC.
authors: Hoong-Chien
authors: HC
authors: Lee
authors: Institute of Biomedical Sciences and Technology, Department of Biochemistry and Molecular Biology, SUNY Upstate Medical University, Syracuse, NY, USA.
authors: David
authors: D
authors: Kakhniashvili
authors: Institute of Biomedical Sciences and Technology, Department of Biochemistry and Molecular Biology, SUNY Upstate Medical University, Syracuse, NY, USA.
authors: Steven R
authors: SR
authors: Goodman
authors: Institute of Molecular Medicine, National Cheng Kung University Medical College, Tainan, Taiwan, ROC.|Institute of Basic Medical Sciences, National Cheng Kung University Medical College, Tainan, Taiwan, ROC.|Center of Infectious Disease and Signal Research, National Cheng Kung University, Tainan, Taiwan, ROC.|Advanced Optoelectronic Technology Center, National Cheng Kung University Medical College, Tainan, Taiwan, ROC.|Department of Neuroscience and Physiology, SUNY Upstate Medical University, Syracuse, NY, USA.
authors: Nan-Shan
authors: NS
authors: Chang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000494:pharmacology*; D000595:Amino Acid Sequence; D000818:Animals; D018941:Antigens, CD19 / Q000276:immunology*; D017252:CD3 Complex / Q000276:immunology*; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000276:immunology*; D058851:GPI-Linked Proteins / Q000235:genetics / Q000276:immunology; D006801:Humans; D006821:Hyaluronoglucosaminidase / Q000235:genetics / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016688:Mice, Inbred NOD; D008819:Mice, Nude; D016513:Mice, SCID; D008969:Molecular Sequence Data; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D010446:Peptide Fragments / Q000494:pharmacology; D013154:Spleen / Q000187:drug effects* / Q000276:immunology* / Q000473:pathology
chemical_list: C466684:APBB2 protein, human; D048868:Adaptor Proteins, Signal Transducing; D018941:Antigens, CD19; D017252:CD3 Complex; D015815:Cell Adhesion Molecules; D058851:GPI-Linked Proteins; D010446:Peptide Fragments; C473096:Hyal2 protein, human; C469221:Hyal2 protein, mouse; D006821:Hyaluronoglucosaminidase