Published online Feb 21, 2014. doi: 10.3748/wjg.v20.i7.1681
Revised: October 1, 2013
Accepted: November 12, 2013
Published online: February 21, 2014
Gastric cancer is the fourth most common cancer, and the second-highest cause of cancer-related deaths worldwide. Despite extensive research to identify novel diagnostic and therapeutic agents, patients with advanced gastric cancer suffer from a poor quality of life and poor prognosis, and treatment is dependent mainly on conventional cytotoxic chemotherapy. To improve the quality of life and survival of gastric cancer patients, a better understanding of the underlying molecular pathologies, and their application towards the development of novel targeted therapies, is urgently needed. Chemokines are a group of small proteins associated with cytoskeletal rearrangements, the directional migration of several cell types during development and physiology, and the host immune response via interactions with G-protein coupled receptors. There is also growing evidence to suggest that chemokines not only play a role in the immune system, but are also involved in the development and progression of tumors. In gastric cancer, CXC chemokines and chemokine receptors regulate the trafficking of cells in and out of the tumor microenvironment. CXC chemokines and their receptors can also directly influence tumorigenesis by modulating tumor transformation, survival, growth, invasion and metastasis, as well as indirectly by regulating angiogenesis, and tumor-leukocyte interactions. In this review, we will focus on the roles of CXC chemokines and their receptors in the development, progression, and metastasis of gastric tumors, and discuss their therapeutic potential for gastric cancer.
Core tip: Chemokines were traditionally believed to regulate the directional migration of leukocytes to inflammatory sites. However, it is now clear that chemokines and chemokine receptors also regulate the processes underlying the development and progression of malignant disease. In gastric cancer, CXC chemokines and their receptors directly influence tumorigenesis by modulating tumor transformation, survival, growth, invasion, and metastasis, as well as indirectly by regulating angiogenesis and interactions between tumor and microenvironment. Aim of this review is to discuss the involvement of CXC chemokines and their receptors in the development, progression, and metastasis of gastric cancer and their therapeutic potential.