RT Journal Article
SR Electronic
T1 A claudin-targeting molecule as an inhibitor of tumor metastasis
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP jpet.110.168070
DO 10.1124/jpet.110.168070
A1 Rie Saeki
A1 Masuo Kondoh
A1 Hideki Kakutani
A1 Kohji Matsuhisa
A1 Azusa Takahashi
A1 Hidehiko Suzuki
A1 Yohei Kakamu
A1 Akihiro Watari
A1 Kiyohito Yagi
YR 2010
UL http://jpet.aspetjournals.org/content/early/2010/05/04/jpet.110.168070.abstract
AB Tumor metastasis of epithelium-derived tumors is the major cause of death from malignant tumors. Overexpression of claudin is frequently observed in malignant tumors. However, claudin-targeting anti-metastasis therapy has never been investigated. We previously prepared a claudin-4-targeting anti-tumor molecule that consisted of the C-terminal fragment of Clostridium perfringens enterotoxin (C-CPE) fused to protein synthesis inhibitory factor (PSIF) derived from Pseudomonas exotoxin. In the present study, we investigated whether claudin CPE receptors can be a target for tumor metastasis by using the C-CPE-fused PSIF as a claudin-targeting agent. One of the most popular murine metastasis models is the lung metastasis of intravenously injected B16 cells. Therefore, we first investigated the effects of the C-CPE-fused PSIF on lung metastasis of claudin-4-expressing B16 cells (CL4-B16 cells). Intravenous administration of the C-CPE-fused PSIF suppressed lung metastasis of CL4-B16 cells but not B16 cells. Injection of C-CPE-fused PSIF also inhibited tumor growth and spontaneous lung metastasis of murine breast cancer 4T1 cells inoculated into the subcutis. Treatment with C-CPE-fused PSIF did not show apparent side effects in mice. These findings indicate that claudin-targeting may be a novel strategy for inhibiting some tumor metastases.The American Society for Pharmacology and Experimental Therapeutics