Cell-permeable NM23 blocks the maintenance and progression of established pulmonary metastasis.

Lim J, Jang G, Kang S, Lee G, Nga do TT, Phuong do TL, Kim H, El-Rifai W, Ruley HE, Jo D
Cancer Res. 2011 71 (23): 7216-25

PMID: 21987726 · DOI:10.1158/0008-5472.CAN-11-2015

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.

MeSH Terms (21)

Amino Acid Sequence Animals Cell-Penetrating Peptides Cell Line, Tumor Cell Movement Disease Progression Female HCT116 Cells Humans Lung Neoplasms Mice Mice, Inbred BALB C Mitogen-Activated Protein Kinase Kinases Molecular Sequence Data Molecular Targeted Therapy Neoplasm Metastasis NIH 3T3 Cells NM23 Nucleoside Diphosphate Kinases Protein Sorting Signals Recombinant Fusion Proteins Xenograft Model Antitumor Assays

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