Targeting Id1 and Id3 inhibits peritoneal metastasis of gastric cancer.
Inhibitor of DNA binding (Id) proteins are essential for cell differentiation, proliferation, migration, invasion and angiogenesis. Recently, they have been shown to correlate with less differentiated phenotypes, high malignant potential and poor clinical outcome in various kinds of tumors. In an attempt to develop new strategies for the treatment of peritoneal metastasis of gastric cancer, we prepared an Id1, 3 double-knockdown gastric cancer cell line, MKN45, by RNA interference and investigated its effects on the development of metastatic nodules in the peritoneal cavity. Both cell proliferation and migration capabilities were decreased in Id1, 3 double-knockdown cells, as was their ability to bind to laminin, which could be explained by the decreased expression of integrin alpha6. These are important steps in the metastatic process. In a mouse model, the number of peritoneal metastatic nodules formed by Id1, 3 double-knockdown cells was reduced compared to mock-transfected control cells, as was the size of individual tumors. In this study, we clearly demonstrated that Id1, 3 double-knockdown significantly impaired the ability of gastric cancer cells to form peritoneal metastasis. Id should be considered an ideal target for the treatment and prevention of gastric cancer, and RNA interference is an attractive and promising strategy to achieve it.
Tsuchiya
Takeshi
T
Department of Surgical Oncology, Faculty of Medicine, the University of Tokyo, Bunkyo-ku, Japan. tk-tsuchiya@muh.biglobe.ne.jp
Okaji
Yurai
Y
Tsuno
Nelson H
NH
Sakurai
Daisuke
D
Tsuchiya
Naoyuki
N
Kawai
Kazushige
K
Yazawa
Kentaro
K
Asakage
Masahiro
M
Yamada
Jun
J
Yoneyama
Satomi
S
Kitayama
Joji
J
Osada
Takuya
T
Watanabe
Toshiaki
T
Tokunaga
Katsushi
K
Takahashi
Koki
K
Nagawa
Hirokazu
H
D000818:Animals; D002465:Cell Movement; D049109:Cell Proliferation; D004195:Disease Models, Animal; D006801:Humans; D051798:Inhibitor of Differentiation Protein 1 / Q000235:genetics* / Q000502:physiology*; D051796:Inhibitor of Differentiation Proteins / Q000235:genetics* / Q000502:physiology*; D051379:Mice; D009362:Neoplasm Metastasis / Q000235:genetics / Q000503:physiopathology; D009363:Neoplasm Proteins / Q000235:genetics* / Q000502:physiology*; D010534:Peritoneal Neoplasms / Q000556:secondary*; D034622:RNA Interference; D013274:Stomach Neoplasms / Q000473:pathology*; D014407:Tumor Cells, Cultured
C497453:ID1 protein, human; D051798:Inhibitor of Differentiation Protein 1; D051796:Inhibitor of Differentiation Proteins; D009363:Neoplasm Proteins; C075640:ID3 protein, human