
Targeting claudin‐4 enhances chemosensitivity of pancreatic ductal carcinomas
Author(s) -
Sasaki Takamitsu,
FujiwaraTani Rina,
Kishi Shingo,
Mori Shiori,
Luo Yi,
Ohmori Hitoshi,
Kawahara Isao,
Goto Kei,
Nishiguchi Yukiko,
Mori Takuya,
Sho Masayuki,
Kondo Masuo,
Kuniyasu Hiroki
Publication year - 2019
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.2547
Subject(s) - claudin , cancer research , biology , immunohistochemistry , downregulation and upregulation , metastasis , extracellular , folfirinox , cell growth , pathology , tight junction , cancer , medicine , microbiology and biotechnology , immunology , biochemistry , genetics , colorectal cancer , gene , irinotecan
Claudin (CLDN) family comprises of protein that form a tight junction, and is involved in regulating polarity and differentiation of cells. Here, we aimed to investigate the effects of inhibiting CLDN4 in pancreatic ductal carcinomas (PDC). We first examined 91 cases of human PDC by immunohistochemistry and found that CLDN4 expression was correlated with tumor invasion, nodal metastasis, and distant metastasis. Anti‐CLDN4 extracellular domain antibody, previously established by us (4D3), inhibited the proliferation of MIA‐PaCa‐2 PDC cells and increased intracellular 5‐fluorouracil (5‐FU) concentration with lowering transepithelial electrical resistance. Concurrent treatment of 5‐FU and 4D3 resulted in synergistic inhibition of growth of MIA‐PaCa‐2 cells in nude mice. In addition, MIA‐PaCa‐2 cell tumors treated with full‐dose folfirinox (FFX) decreased tumor diameters to 50%; however, 60% of mice were dead from adverse effects. In contrast, half‐dose FFX concomitant with 4D3 treatment decreased tumors equivalent to full‐dose FFX, but without the adverse effects. These findings suggest that targeting CLDN4 might increase the effectiveness and safety of anticancer drug therapy in PDC.