Chlorotoxin-Fc fusion inhibits release of MMP-2 from pancreatic cancer cells

Samah El-Ghlban, Tomonari Kasai, Tsukasa Shigehiro, Hong Xia Yin, Sreeja Sekhar, Mikiko Ida, Anna Sanchez, Akifumi Mizutani, Takayuki Kudoh, Hiroshi Murakami, Masaharu Seno

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Abstract

Chlorotoxin (CTX) is a 36-amino acid peptide derived from Leiurus quinquestriatus (scorpion) venom, which inhibits low-conductance chloride channels in colonic epithelial cells. It has been reported that CTX also binds to matrix metalloproteinase-2 (MMP-2), membrane type-1 MMP, and tissue inhibitor of metalloproteinase-2, as well as CLC-3 chloride ion channels and other proteins. Pancreatic cancer cells require the activation of MMP-2 during invasion and migration. In this study, the fusion protein was generated by joining the CTX peptide to the amino terminus of the human IgG-Fc domain without a hinge domain, the monomeric form of chlorotoxin (M-CTX-Fc). The resulting fusion protein was then used to target pancreatic cancer cells (PANC-1) in vitro. M-CTX-Fc decreased MMP-2 release into the media of PANC-1 cells in a dose-dependent manner. M-CTX-Fc internalization into PANC-1 cells was observed. When the cells were treated with chlorpromazine (CPZ), the internalization of the fusion protein was reduced, implicating a clathrin-dependent internalization mechanism of M-CTX-Fc in PANC-1 cells. Furthermore, M-CTX-Fc clearly exhibited the inhibition of the migration depending on the concentration, but human IgG, as negative control of Fc, was not affected. The M-CTX-Fc may be an effective instrument for targeting pancreatic cancer.

Original languageEnglish
Article number152659
JournalBioMed Research International
Volume2014
DOIs
Publication statusPublished - 2014

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Medicine(all)

Cite this

El-Ghlban, S., Kasai, T., Shigehiro, T., Yin, H. X., Sekhar, S., Ida, M., Sanchez, A., Mizutani, A., Kudoh, T., Murakami, H., & Seno, M. (2014). Chlorotoxin-Fc fusion inhibits release of MMP-2 from pancreatic cancer cells. BioMed Research International, 2014, [152659]. https://doi.org/10.1155/2014/152659