Controlled secretion of the anticancer protein MDA-7 from engineered mesenchymal stem cells

Atsunobu Sagara, Takeshi Karasawa, Katsuhide Igarashi, Maky Otsuka, Rei Sugiura, Akihiro Kodama, Mutsumi Yamashita, Minoru Narita, Yoshinori Kato

Research output: Contribution to journalArticle

Abstract

Mesenchymal stem cells (MSCs) have been explored as a "live" carrier of cytokines for targeted cancer therapy, but, in earlier reports in the literature, the secretion process of therapeutic cytokines was not regulated. The purpose of this study was to generate MSCs to conditionally secrete the melanoma differentiationassociated gene-7 (MDA-7) tumor-suppressor protein. To control the secretion of MDA-7 from MSCs, a wellestablished tetracycline-controlled transcriptional activation system was incorporated into MDA-7 plasmid. MDA-7 gene expression was induced in the engineered MSCs only in the presence of doxycycline, as characterized by quantitative reverse transcription (qRT)-PCR. Enzyme-linked immunosorbent assay (ELISA) also revealed that the MDA-7 protein was secreted from the engineered MSCs only after the cells had been exposed to doxycycline. Both recombinant human MDA-7 protein and the conditioned medium from the engineered MSCs in the presence of doxycycline significantly inhibited tube formation of human umbilical vascular endothelial cells (HUVECs), indicating that our system could be used for targeted, antiangiogenic therapy. Overall, this study provides useful information on the potential use of engineered MSCs for the controlled secretion of therapeutic proteins, in this case MDA-7, for targeted cancer therapy.

Original languageEnglish (US)
Pages (from-to)113-117
Number of pages5
JournalBiological and Pharmaceutical Bulletin
Volume40
Issue number1
StatePublished - 2017
Externally publishedYes

Keywords

  • Controlled secretion
  • In vitro
  • Melanoma differentiation-associated gene-7
  • Mesenchymal stem cell
  • Tet-On system

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

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  • Cite this

    Sagara, A., Karasawa, T., Igarashi, K., Otsuka, M., Sugiura, R., Kodama, A., Yamashita, M., Narita, M., & Kato, Y. (2017). Controlled secretion of the anticancer protein MDA-7 from engineered mesenchymal stem cells. Biological and Pharmaceutical Bulletin, 40(1), 113-117.