Beneficial influence of microsatellite instability on gelatinase-tissue inhibitors of metalloproteinase balance in colorectal cancer
Thiéfin, Gérard.; Dupont, Aélie.; Guillou, P-José.; Vitry, F.; Bouche, O.; Yaziji, N.; Lagarde, Séphanie.; Maquart, Fçois-Xavier.; Palot, J-Pierre.; Hornebeck, W.; Diebold, M-Danièle.
Anticancer Research 27(1b): 583-588
2007
ISSN/ISBN: 0250-7005 PMID: 17348445 Document Number: 605504
Background: Colorectal cancers (CRC) with high level of microsatellite instability (MSI-H) are characterized by lower metastasis propensity and better prognosis than their stable microsatellite (MSS) counterpart. It was hypothesized that the difference in cancer progression might be related to distinct gelatinase-tissue inhibitors of metalloproteinase (TIMPs) balance in MSI-H and MSS sporadic CRC. Patients and Methods: Levels of gelatinase-A (MMP-2) and -B (MMP-9), TIMP-1 and -2 and membrane-type matrix metalloproteinase-1 (MT1-MMP) were compared in tumors and normal mucosa from patients with MSI-H and MSS CRC. Results: Active levels of MMP-2 and -9, normalized to normal mucosa, were lower in MSI-H than MSS CRC. There was a trend for higher levels of TIMP-1 and TIMP-2 within MSI-H tumors compared with MSS tumors (p=0.08 and p=0.15, respectively), while TIMP-2 amounts were significantly higher in adjacent normal tissue (p < 0.001) inpatients with MSI-Hvs. MSS cancers. There was also a trend for lower MT1-MMP activity in MSI-H than in MSS CRC. Conclusion: Our data suggest that the distinct invasive and metastatic behaviors of MSI-H and MSS CRC may be related to different patterns of gelatinase secretion and regulation.