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Uchihara et al. J Cancer Metastasis Treat 2018;4:9 Journal of Cancer
DOI: 10.20517/2394-4722.2017.81 Metastasis and Treatment

Review Open Access

Therapeutic targets against gastric cancer stem
cells interacting with tumor microenvironment

Tomoyuki Uchihara, Takatsugu Ishimoto, Atsuko Yonemura, Hideo Baba

Department of Gastroenterological Surgery, Graduate School of Medical Science, Kumamoto University, Kumamoto 860-8556,
Japan.
Correspondence to: Prof. Hideo Baba, Department of Gastroenterological Surgery, Graduate School of Medical Science, Kumamoto
University, Kumamoto 860-8556, Japan. E-mail: hdobaba@kumamoto-u.ac.jp
How to cite this article: Uchihara T, Ishimoto T, Yonemura A, Baba H. Therapeutic targets against gastric cancer stem cells interacting
with tumor microenvironment. J Cancer Metastasis Treat 2018;4:9. http://dx.doi.org/10.20517/2394-4722.2017.81
Received: 21 Nov 2017 First Decision: 5 Jan 2018 Revised: 22 Jan 2018 Accepted: 22 Jan 2018 Published: 26 Feb 2018

Science Editor: Masayuki Watanabe Copy Editor: Jun-Yao Li Production Editor: Huan-Liang Wu

Abstract
Gastric cancer (GC) is a major cause of cancer-related deaths worldwide. The existence of cancer stem cells (CSCs) is
known to be the main reason for resistance to anticancer agents as well as for the development of distant metastases.
Although CSCs themselves harbor self-renewal and differentiation abilities, the tumor microenvironment that surrounds
CSCs provides secreted factors and supports angiogenesis and is thus responsible for the maintenance of their CSC
properties. The current review provides information regarding the impact of the tumor microenvironment on gastric CSCs,
which will support the development of novel therapeutic strategies for targeting gastric CSCs.

Keywords: Gastric cancer stem cells, stem cell markers, tumor microenvironment, gastric cancer treatment

INTRODUCTION
Although the proportion of individuals with gastric cancer (GC) has declined for decades, GC continues to
[1-3]
be a major cause of cancer-related deaths worldwide . Despite improvements in the treatment of GC, the
clinical outcome of patients with advanced GC after curative resection is still poor, which is mainly due to
[4]
recurrence and metastasis . Therefore, new treatment options for this disease must be developed.

Recent evidence has increasingly indicated that the heterogeneity of the tumor is a consequence of cancer
[5-7]
stem cells (CSCs), which are deeply involved in tumor progression and metastasis . Malignant tumors have
[8]
been reported to exhibit obvious histologic heterogeneity. In 1937, Furth et al. demonstrated that a single
leukemia cell could cause systemic disease in recipient mice. However, it took a long time for the concept of

© The Author(s) 2018. Open Access This article is licensed under a Creative Commons Attribution 4.0
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