Published online Mar 21, 2015. doi: 10.3748/wjg.v21.i11.3206
Peer-review started: July 24, 2014
First decision: August 15, 2014
Revised: November 13, 2014
Accepted: December 16, 2014
Article in press: December 16, 2014
Published online: March 21, 2015
There are 33 human tetraspanin proteins, emerging as key players in malignancy, the immune system, fertilization, cellular signaling, adhesion, morphology, motility, proliferation, and tumor invasion. CD9, a member of the tetraspanin family, associates with and influences a variety of cell-surface molecules. Through these interactions, CD9 modifies multiple cellular events, including adhesion, migration, proliferation, and survival. CD9 is therefore considered to play a role in several stages during cancer development. Reduced CD9 expression is generally related to venous vessel invasion and metastasis as well as poor prognosis. We found that treatment of mice bearing human gastric cancer cells with anti-CD9 antibody successfully inhibited tumor progression via antiproliferative, proapoptotic, and antiangiogenic effects, strongly indicating that CD9 is a possible therapeutic target in patients with gastric cancer. Here, we describe the possibility of CD9 manipulation as a novel therapeutic strategy in gastric cancer, which still shows poor prognosis.
Core tip: Tetraspanin CD9 is a cell-surface protein with four transmembrane domains and is found in several organs. Although CD9 was primarily identified as a tumor suppressor, it exhibits diverse functions through its association with various partner proteins. CD9 relates to tumor proliferation, apoptosis, migration, adhesion, and angiogenesis, therefore involving several steps of tumor formation: communication with the environment, dissemination, and metastasis. In this review, we describe the possibility of CD9 manipulation as a novel therapeutic strategy to improve clinical outcome in gastric cancer.