Differences in the gene expression profile of matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) in primary colorectal tumors and their synchronous liver metastases.
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.
Gentner
Bernhard
B
Department of Medicine, Friedrich Alexander University Erlangen-Nuremberg, Erlangen, Germany.
Wein
Axel
A
Croner
Roland S
RS
Zeittraeger
Isabel
I
Wirtz
Ralph M
RM
Roedel
Franz
F
Dimmler
Arno
A
Dorlaque
Laure
L
Hohenberger
Werner
W
Hahn
Eckhart G
EG
Brueckl
Wolfgang M
WM