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

Research output: Contribution to journalArticle

10 Citations (Scopus)

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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Matrix Metalloproteinase 2
Pancreatic Neoplasms
Fusion reactions
Cells
Chloride Channels
Matrix Metalloproteinase 15
Proteins
Immunoglobulin G
Chlorotoxin
Scorpion Venoms
Matrix Metalloproteinase 14
Tissue Inhibitor of Metalloproteinase-2
Clathrin
Peptides
Matrix Metalloproteinase Inhibitors
Chlorpromazine
Hinges
Matrix Metalloproteinases
Joining
Epithelial Cells

ASJC Scopus subject areas

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

Cite this

Chlorotoxin-Fc fusion inhibits release of MMP-2 from pancreatic cancer cells. / El-Ghlban, Samah; Kasai, Tomonari; Shigehiro, Tsukasa; Yin, Hong Xia; Sekhar, Sreeja; Ida, Mikiko; Sanchez, Anna; Mizutani, Akifumi; Kudoh, Takayuki; Murakami, Hiroshi; Seno, Masaharu.

In: BioMed Research International, Vol. 2014, 152659, 2014.

Research output: Contribution to journalArticle

El-Ghlban, S, Kasai, T, Shigehiro, T, Yin, HX, 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, vol. 2014, 152659. https://doi.org/10.1155/2014/152659
El-Ghlban, Samah ; Kasai, Tomonari ; Shigehiro, Tsukasa ; Yin, Hong Xia ; Sekhar, Sreeja ; Ida, Mikiko ; Sanchez, Anna ; Mizutani, Akifumi ; Kudoh, Takayuki ; Murakami, Hiroshi ; Seno, Masaharu. / Chlorotoxin-Fc fusion inhibits release of MMP-2 from pancreatic cancer cells. In: BioMed Research International. 2014 ; Vol. 2014.
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