Thiéfin Gérard, Dupont Aurélie, Guillou Pierre-José, Vitry Fabien, Bouche Olivier, Yaziji Nahla, Lagarde Stéphanie, Maquart François-Xavier, Palot Jean-Pierre, Hornebeck William, Diebold Marie-Danièle
CHU Reims, Hôpital Robert Debré, Service d'Hépato-Gastroentérologie, Reims F-51092, France.
Anticancer Res. 2007 Jan-Feb;27(1B):583-8.
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.
Levels of gelatinase-A (MMP-2) and -B (MMP-9), TIMP-1 and -2 and membrane-type matrix metallo-proteinase-1 (MT1-MMP) were compared in tumors and normal mucosa from patients with MSI-H and MSS CRC.
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) in patients with MSI-H vs. MSS cancers. There was also a trend for lower MT1-MMP activity in MSI-H than in MSS CRC.
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.
微卫星高度不稳定（MSI-H）的结直肠癌（CRC）与微卫星稳定（MSS）的结直肠癌相比，具有较低的转移倾向和较好的预后。据推测，癌症进展的差异可能与MSI-H和MSS散发性CRC中金属蛋白酶组织抑制剂（TIMP）与明胶酶的不同平衡有关。
比较了MSI-H和MSS CRC患者肿瘤组织和正常黏膜中明胶酶-A（MMP-2）、明胶酶-B（MMP-9）、TIMP-1、TIMP-2和膜型基质金属蛋白酶-1（MT1-MMP）的水平。
与MSS CRC相比，MSI-H CRC中以正常黏膜为参照的MMP-2和MMP-9活性水平较低。与MSS肿瘤相比，MSI-H肿瘤中TIMP-1和TIMP-2水平有升高趋势（分别为p=0.08和p=0.15），而在MSI-H癌症患者与MSS癌症患者中，相邻正常组织中的TIMP-2含量显著更高（p<0.001）。与MSS CRC相比，MSI-H中MT1-MMP活性也有降低趋势。
我们的数据表明，MSI-H和MSS CRC不同的侵袭和转移行为可能与明胶酶分泌和调控的不同模式有关。
