Review
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jan 14, 2016; 22(2): 833-841
Published online Jan 14, 2016. doi: 10.3748/wjg.v22.i2.833
Chemokine/chemokine receptor pair CCL20/CCR6 in human colorectal malignancy: An overview
Vilma Oliveira Frick, Claudia Rubie, Ulrich Keilholz, Pirus Ghadjar
Vilma Oliveira Frick, Claudia Rubie, Department of General-, Visceral-, Vascular- and Pediatric Surgery, University of the Saarland, 66421 Homburg/Saar, Germany
Ulrich Keilholz, Charité Comprehensive Cancer Center, Charité Universitätsmedizin Berlin, Campus Charité Mitte, 10117 Berlin, Germany
Pirus Ghadjar, Department of Radiation Oncology, Charité Universitätsmedizin Berlin, 13353 Berlin, Germany
Author contributions: Frick VO drafted the manuscript; Rubie C, Ghadjar P and Keilholz U revised the manuscript for important intellectual content.
Conflict-of-interest statement: The authors declare no conflict of interest.
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: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Vilma Oliveira Frick, PhD, Department of General-, Visceral-, Vascular- and Pediatric Surgery, University of the Saarland, Building 57, 66421 Homburg/Saar, Germany. vilma.frick@uks.eu
Telephone: +49-6841-47867
Received: March 27, 2015
Peer-review started: March 30, 2015
First decision: June 25, 2015
Revised: July 17, 2015
Accepted: November 9, 2015
Article in press: November 9, 2015
Published online: January 14, 2016
Abstract

Chemokines belong to a superfamily of small, cytokine-like proteins, which induce multiple physiological functions, particularly cytoskeletal rearrangement and compartment-specific migration through their interaction with G-protein-coupled receptors. Chemokines and their receptors have been widely acknowledged as essential and selective mediators in leukocyte migration in inflammatory response. It is now established that the chemokine/chemokine receptor system is also used by cancer cells to direct lymphatic and haematogenous spreading and additionally has an impact on the site of metastatic growth of different tumours. In recent years an increasing number of studies have drawn attention to CC-chemokine cysteine motif chemokine ligand 20 (CCL20) and its physiological sole receptor CCR6 to play a role in the onset, development and metastatic spread of various gastrointestinal cancer entities. Among various cancer types CCR6 was also demonstrated to be significantly overexpressed in colorectal cancer (CRC) and stimulation by its physiological ligand CCL20 has been reported to promote CRC cell proliferation and migration in vitro. Further, the CCL20/CCR6 system apparently plays a role in the organ-selective liver metastasis of CRC. Here we review the literature on expression patterns of CCL20 and CCR6 and their physiological interactions as well as the currently presumed role of CCL20 and CCR6 in the formation of CRC and the development of liver metastasis, providing a potential basis for novel treatment strategies.

Keywords: Chemokine/chemokine receptor pair, CCR6, Chemokine ligand 20, Colorectal cancer, Metastasis, Liver

Core tip: Here we review the current literature published with respect to the expression pattern of chemokine/chemokine receptor pair cysteine motif chemokine ligand 20 (CCL20)/CCR6 and their physiological interactions as well as the currently presumed role of the CCL20/CCR6 system in the onset and development of colorectal cancer (CRC) and its apparent role in the organ-selective metastatic spread of CRC cells to the liver. Disrupting the chemokine/chemokine receptor interaction of CCL20/CCR6 may therefore be a promising novel treatment strategy in CRC and metastasis.