Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Mar 21, 2015; 21(11): 3206-3213
Published online Mar 21, 2015. doi: 10.3748/wjg.v21.i11.3206
Novel CD9-targeted therapies in gastric cancer
Yoko Murayama, Kenji Oritani, Shusaku Tsutsui
Yoko Murayama, Shusaku Tsutsui, Department of Gastroenterology and Hepatology, Itami City Hospital, Itami 664-8540, Japan
Kenji Oritani, Department of Hematology/Oncology, Graduate School of Medicine, Osaka University, Suita 565-0871, Japan
Author contributions: Murayama Y was responsible for the literature review, and preparation of the manuscript; Oritani K prepared the final version of the manuscript; Tsutsui S provided intellectual support.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Yoko Murayama, MD, PhD, Department of Gastroenterology and Hepatology, Itami City Hospital, 1-100 Koyaike, Itami 664-8540, Japan.
Telephone: +81-72-7773773 Fax: +81-72-7819888
Received: July 23, 2014
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.

Keywords: CD9, Tetraspanin, Gastric cancer, Tumorigenicity, Therapeutic target

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.