CCR6/CCL20 chemokine expression profile in distinct colorectal malignancies

Scand J Immunol. 2013 Sep;78(3):298-305. doi: 10.1111/sji.12087.

Abstract

Originally, chemokines and their G-protein-coupled receptors were described to regulate multiple physiological functions, particularly tissue architecture and compartment-specific migration of white blood cells. Now, it is established that the chemokine/chemokine receptor system is also used by cancer cells for migration and metastatic spread. Here, we examined the relative levels of CC-chemokine CCL20 and its corresponding receptor CCR6 in resection specimens from patients with different malignant and non-malignant colorectal diseases as well as in colorectal liver metastases (CRLM). CCL20/CCR6 mRNA and protein expression profiles were assessed by quantitative real-time PCR (qRT-PCR), enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry (IHC) in resection specimens from patients with ulcerative colitis (UC, n = 15), colorectal adenoma (CRA, n = 15), colorectal adenocarcinoma (CRC, n = 61) and colorectal liver metastases (CRLM, n = 16). Corresponding non-diseased tissues served as control. In contrast to UC tissues, the CCL20/CCR6 system showed a distinct upregulation in CRA, CRC and CRLM related to corresponding non-affected tissues (P < 0.05, respectively). Furthermore, CRA, CRC and CRLM tissue samples displayed significantly higher protein amounts of CCL20 in comparison with UC specimens (P < 0.05, respectively). Our results strongly suggest an association between CCL20/CCR6 expression and the induction of CRA, CRC and the development of CRLM. Therefore, CCL20 and CCR6 may provide potential targets for novel treatment strategies of CRC.

MeSH terms

  • Adenocarcinoma / immunology
  • Adenocarcinoma / metabolism
  • Adenoma / immunology
  • Adenoma / metabolism
  • Adult
  • Aged
  • Chemokine CCL20 / metabolism*
  • Colitis, Ulcerative / immunology
  • Colitis, Ulcerative / metabolism*
  • Colorectal Neoplasms / immunology*
  • Colorectal Neoplasms / metabolism*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Liver Neoplasms / immunology
  • Liver Neoplasms / metabolism*
  • Liver Neoplasms / secondary
  • Male
  • Middle Aged
  • Receptors, CCR6 / metabolism*

Substances

  • CCL20 protein, human
  • CCR6 protein, human
  • Chemokine CCL20
  • Receptors, CCR6