title: Effect of preoperative FOLFOX chemotherapy on CCL20/CCR6 expression in colorectal liver metastases.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of General, Visceral, Vascular and Paediatric Surgery, University of the Saarland, Homburg/Saar, Germany. ca.labor@uks.eu
authors.forename: Claudia
authors.initials: C
authors.lastname: Rubie
authors.forename: Vilma Oliveira
authors.initials: VO
authors.lastname: Frick
authors.forename: Pirus
authors.initials: P
authors.lastname: Ghadjar
authors.forename: Mathias
authors.initials: M
authors.lastname: Wagner
authors.forename: Christoph
authors.initials: C
authors.lastname: Justinger
authors.forename: Stefan
authors.initials: S
authors.lastname: Graeber
authors.forename: Jens
authors.initials: J
authors.lastname: Sperling
authors.forename: Otto
authors.initials: O
authors.lastname: Kollmar
authors.forename: Martin K
authors.initials: MK
authors.lastname: Schilling
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D054418:Chemokine CCL20 / Q000235:genetics / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology*; D005472:Fluorouracil / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D019394:Ki-67 Antigen / Q000235:genetics / Q000378:metabolism; D002955:Leucovorin / Q000494:pharmacology / Q000627:therapeutic use; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000556:secondary* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000494:pharmacology / Q000627:therapeutic use; D057234:Preoperative Period; D054399:Receptors, CCR6 / Q000235:genetics / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; C108355:CCL20 protein, human; C106311:CCR6 protein, human; D054418:Chemokine CCL20; D019394:Ki-67 Antigen; D009944:Organoplatinum Compounds; D054399:Receptors, CCR6; D002955:Leucovorin; D005472:Fluorouracil