title: Differences in the gene expression profile of matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) in primary colorectal tumors and their synchronous liver metastases.
abstract: BACKGROUND
  Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) have been strongly implicated in the pathogenesis of many types of human cancer. We wanted to specifically define their role in established colorectal cancer liver metastases.
  
  
  METHODS
  The MMP/TIMP expression profiles of N=9 colorectal primary tumour liver metastasis tissue pairs were determined using oligonucleotide-based arrays. Expression levels for the most relevant MMPs were confirmed by reverse-transcriptase polymerase chain reaction (RT-PCR). Additionally, unsupervised clustering using the MMP/TIMP profile of N=25 colorectal cancer liver metastases was performed and the response to palliative 5-fluorouracil (5-FU)-based chemotherapy was assessed using radiological response criteria.
  
  
  RESULTS
  When comparing the primary tumors to their synchronous liver metastases, a statistically significant (p < 0.05) down-regulation of MMP1, -2, -3 and -12 was found in the metastases. Unsupervised clustering using the MMP/TIMP profiles of 25 liver metastases revealed two distinct subgroups with different responses to palliative, 5-FU-based chemotherapy (response rates: 22% vs. 56%, respectively). In particular, higher MMP7, TIMP1 and TIMP2 levels were found in the unfavourable group, while higher expression of MMP2, -9, -11 and -14 was associated with a more favourable response to chemotherapy.
  
  
  CONCLUSIONS
  Colorectal cancer liver metastases show a distinctive MMP/TIMP profile with predictive implications.
authors.affiliation: Department of Medicine, Friedrich Alexander University Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Gentner
authors.forename: Axel
authors.initials: A
authors.lastname: Wein
authors.forename: Roland S
authors.initials: RS
authors.lastname: Croner
authors.forename: Isabel
authors.initials: I
authors.lastname: Zeittraeger
authors.forename: Ralph M
authors.initials: RM
authors.lastname: Wirtz
authors.forename: Franz
authors.initials: F
authors.lastname: Roedel
authors.forename: Arno
authors.initials: A
authors.lastname: Dimmler
authors.forename: Laure
authors.initials: L
authors.lastname: Dorlaque
authors.forename: Werner
authors.initials: W
authors.lastname: Hohenberger
authors.forename: Eckhart G
authors.initials: EG
authors.lastname: Hahn
authors.forename: Wolfgang M
authors.initials: WM
authors.lastname: Brueckl