chemokine/chemokine receptor pair CC L20/CC R6 in humancolorectal malignancy:An overview

Chemokines belong to a superfamily of small, cytokinelike 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.

Effect of preoperative FOLFOX chemotherapy on CCL20/CCR6 expression in colorectal liver metastases

AIM:To evaluate the influence of preoperative FOLFOX chemotherapy on CCL20/CCR6 expression in liver metastases of stage Ⅳ colorectal cancer(CRC) patients.METHODS:Using Real Time-PCR,enzyme-linked immunosorbent assay,Western Blots and immunohistochemistry,we have analyzed the expression of CCL20,CCR6 and proliferation marker Ki-67 in colorectal liver metastasis(CRLM) specimens from stage Ⅳ CRC patients who received preoperative FOLFOX chemotherapy(n = 53) and in patients who did not receive FOLFOX chemotherapy prior to liver surgery(n = 29).RESULTS:Of the 53 patients who received FOLFOX,time to liver surgery was ≤ 1 mo in 14 patients,≤ 1 year in 22 patients and > 1 year in 17 patients,respectively.In addition,we investigated the proliferation rate of CRC cells in liver metastases in the different patient groups.Both CCL20 and CCR6 mRNA and protein expression levels were significantly increased in patients who received preoperative FOLFOX chemotherapy ≤ 12 mo before liver surgery(P < 0.001) in comparison to patients who did not undergo FOLFOX treatment.Further,proliferation of CRLM cells as measured by Ki-67 was increased in patients who underwent FOLFOX treatment.CCL20 and CCR6 expression levels were significantly increased in CRLM patients who had undergone preoperative FOLFOX chemotherapy.CONCLUSION:This chemokine/receptor up-regulation could lead to increased proliferation/migration through an autocrine mechanism which might be used by surviving metastatic cells to escape cell death caused by FOLFOX.