Open AccessHypoxia‐mediated CD 24 expression is correlated with gastric cancer aggressiveness by promoting cell migration and invasion
Author(s) -
Fujikuni Nobuaki,
Yamamoto Hideki,
Tanabe Kazuaki,
Naito Yutaka,
Sakamoto Naoya,
Tanaka Yuka,
Yanagihara Kazuyoshi,
Oue Naohide,
Yasui Wataru,
Ohdan Hideki
Publication year - 2014
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.12522
Subject(s) - cd24 , cancer cell , cancer research , cd44 , cancer , biology , gene silencing , gene knockdown , downregulation and upregulation , cell , hypoxia (environmental) , metastasis , immunology , cell culture , chemistry , gene , genetics , organic chemistry , oxygen
CD 24 is a heavily glycosylated cell surface protein that is expressed in putative stem cells and is overexpressed in various human malignancies, yet the significant roles of CD 24 in gastric cancer development are still elusive. We investigated the involvement of CD 24 in gastric cancer aggressiveness, which is attributed to its heterogeneity. Cultured gastric cancer cells showed diverse expression patterns in CD 24, whereas other defined cell surface markers, such as CD 44 and CD 133, were homogenous. Purely sorted CD 24‐negative gastric cancer cells showed strong alteration into the CD 24‐positive cell type in an autochthonous manner, and reached to steady expression levels. Our clinicopathological study revealed that CD 24 positivity was an independent prognostic factor in both intestinal and diffuse types of gastric cancer. CD 24 expression was correlated with the advanced stages, invasiveness, and lymph node metastasis of gastric cancer. Silencing of CD 24 in cultured cells significantly decreased cell migration and invasion. Hypoxic treatment upregulated CD 24 expression, and simultaneously induced cell motility and invasion of gastric cancer cells. Hypoxic treatment‐induced CD 24 expression was significantly attenuated by knockdown of hypoxia‐inducible transcription factors. These data suggest that CD 24‐negative cells are capable of gaining cell motility and invasiveness through the induction of CD 24, which is mediated by hypoxia. CD 24 would be an attractive marker to define not only the heterogeneity but also the aggressiveness of gastric cancer cells. The mechanisms by which hypoxia induces CD 24 expression would also be a potential therapeutic target for gastric cancer.