title: Tumor-suppressive effects of atelocollagen-conjugated hsa-miR-520d-5p on un-differentiated cancer cells in a mouse xenograft model.
abstract: We previously demonstrated that hsa-miR-520d-5p can convert cancer cells into induced pluripotent stem cells (iPSCs) or mesenchymal stem cells (MSCs) via a demethylation process and p53 upregulation in vivo. Additionally, we have reported the non-tumorigenic effect of miR-520d-5p on normal human cells, including fibroblasts.
  
  
  
  We used atelocollagen-conjugated miR-520d-5p (520d/atelocollagen) to confirm the possibility of a therapeutic effect on cancer cells. We traced the size and signal intensity of GFP-expressing tumors in mice each week, beginning 4 weeks after subcutaneous inoculation.
  
  
  
  520d/atelocollagen treatment suppressed tumor growth by greater than 80 % each week relative to controls and resulted in an approximately 30 % disappearance of tumors. In mice whose tumors disappeared, the existence of human genomic material at the injection site was examined by quantitative Alu-PCR, and we confirmed the co-existence of both species-derived cells. In every site where a tumor disappeared in immunodeficient mice, GFP protein was expressed in the connective tissues, and approximately 0.1 % of the extracted DNA contained human genomic material. We could not identify any adverse effects in vivo.
  
  
  
  This is the first report to confirm an inhibitory effect of 520d/atelocollagen on cancer cells in vivo. The development of optimized modifications of this carrier is expected to enhance the efficiency of entry into tumor cells and the induction of its inhibitory effect.
authors.affiliation: Division of Pharmacotherapeutics, Department of Pathophysiological & Therapeutic Science, Faculty of Medicine, Tottori University, 86 Nishicho, Yonago, Tottori, 683-8503, Japan.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Ishihara
authors.affiliation: Division of Pharmacotherapeutics, Department of Pathophysiological & Therapeutic Science, Faculty of Medicine, Tottori University, 86 Nishicho, Yonago, Tottori, 683-8503, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Tsuno
authors.affiliation: Division of Molecular Pathology, Faculty of Medicine, Tottori University, 86 Nishicho, Yonago, Tottori, 683-8503, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kuwamoto
authors.affiliation: Department of Gastroenterology, Tottori University Hospital, 86 Nishicho, Yonago, Tottori, 683-8504, Japan.
authors.forename: Taro
authors.initials: T
authors.lastname: Yamashita
authors.affiliation: Division of Pharmacotherapeutics, Department of Pathophysiological & Therapeutic Science, Faculty of Medicine, Tottori University, 86 Nishicho, Yonago, Tottori, 683-8503, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Endo
authors.affiliation: PEZY-Pharma, 86 Nishicho, Yonago, Tottori, 683-8503, Japan.
authors.forename: Keigo
authors.initials: K
authors.lastname: Miura
authors.affiliation: Orthopedic Surgery, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.
authors.forename: Yugo
authors.initials: Y
authors.lastname: Miura
authors.affiliation: Division of Neurobiology, School of Life Science, Faculty of Medicine, Tottori University, 86 Nishicho, Yonago, Tottori, 683-8503, Japan.
authors.forename: Takemasa
authors.initials: T
authors.lastname: Sato
authors.affiliation: Division of Pharmacotherapeutics, Department of Pathophysiological & Therapeutic Science, Faculty of Medicine, Tottori University, 86 Nishicho, Yonago, Tottori, 683-8503, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Hasegawa
authors.affiliation: Division of Pharmacotherapeutics, Department of Pathophysiological & Therapeutic Science, Faculty of Medicine, Tottori University, 86 Nishicho, Yonago, Tottori, 683-8503, Japan. mnmiura@med.tottori-u.ac.jp.
authors.forename: Norimasa
authors.initials: N
authors.lastname: Miura
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003094:Collagen / Q000008:administration & dosage* / Q000378:metabolism; D004337:Drug Carriers; D015972:Gene Expression Regulation, Neoplastic; D015316:Genetic Therapy; D006801:Humans; D007279:Injections, Subcutaneous; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009369:Neoplasms / Q000235:genetics / Q000628:therapy*; D014183:Transplantation, Heterologous; D023041:Xenograft Model Antitumor Assays
chemical_list: D004337:Drug Carriers; C575048:MIRN520 microRNA, human; D035683:MicroRNAs; C059821:atelocollagen; D003094:Collagen
keywords: Atelocollagen; Cancer; Therapeutic effect; Xenograft model; miR-520d-5p