title: RETRACTED: Cell-permeable NM23 blocks the maintenance and progression of established pulmonary metastasis.
abstract: Occult metastases are a major cause of cancer mortality, even among patients undergoing curative resection. Therefore, practical strategies to target the growth and persistence of already established metastases would provide an important advance in cancer treatment. Here, we assessed the potential of protein therapy using a cell permeable NM23-H1 metastasis suppressor protein. Hydrophobic transduction domains developed from a screen of 1,500 signaling peptide sequences enhanced the uptake of the NM23 protein by cultured cells and systemic delivery to animal tissues. The cell-permeable (CP)-NM23 inhibited metastasis-associated phenotypes in tumor cell lines, blocked the establishment of lung metastases, and cleared already established pulmonary metastases, significantly prolonging the survival of tumor-bearing animals. Therefore, these results establish the potential use of cell-permeable metastasis suppressors as adjuvant therapy against disseminated cancers.
authors: ProCell R&D Institute, ProCell Therapeutics, Inc., Seoul, Korea.
authors: Junghee
authors: J
authors: Lim
authors: Giyong
authors: G
authors: Jang
authors: Seeun
authors: S
authors: Kang
authors: Guewha
authors: G
authors: Lee
authors: Do Thi Thuy
authors: do TT
authors: Nga
authors: Do Thi Lan
authors: do TL
authors: Phuong
authors: Hyuncheol
authors: H
authors: Kim
authors: Wael
authors: W
authors: El-Rifai
authors: H Earl
authors: HE
authors: Ruley
authors: Daewoong
authors: D
authors: Jo
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D057846:Cell-Penetrating Peptides / Q000235:genetics / Q000493:pharmacokinetics / Q000494:pharmacology; D018450:Disease Progression; D005260:Female; D045325:HCT116 Cells; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D008969:Molecular Sequence Data; D058990:Molecular Targeted Therapy / Q000379:methods; D041681:NIH 3T3 Cells; D054778:NM23 Nucleoside Diphosphate Kinases / Q000235:genetics / Q000493:pharmacokinetics / Q000494:pharmacology*; D009362:Neoplasm Metastasis; D021382:Protein Sorting Signals; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000493:pharmacokinetics / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays
chemical_list: D057846:Cell-Penetrating Peptides; D054778:NM23 Nucleoside Diphosphate Kinases; D021382:Protein Sorting Signals; D011993:Recombinant Fusion Proteins; D020929:Mitogen-Activated Protein Kinase Kinases