Differences in the gene expression profile of matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) in primary colorectal tumors and their synchronous liver metastases.
Anticancer Res
; 29(1): 67-74, 2009 Jan.
Article
en En
| MEDLINE
| ID: mdl-19331134
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. PATIENTS ANDMETHODS:
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.CONCLUSION:
Colorectal cancer liver metastases show a distinctive MMP/TIMP profile with predictive implications.
Buscar en Google
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias Colorrectales
/
Inhibidores Tisulares de Metaloproteinasas
/
Metaloproteinasas de la Matriz
/
Neoplasias Hepáticas
Tipo de estudio:
Prognostic_studies
Límite:
Adult
/
Aged
/
Aged80
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Anticancer Res
Año:
2009
Tipo del documento:
Article
País de afiliación:
Alemania