Matrix metalloproteinases, their tissue inhibitors and colorectal cancer staging
Matrix metalloproteinases, their tissue inhibitors and colorectal cancer staging
复制标题
DOI：
10.1046/j.1365-2168.2000.01531.x
复制
发表时间：
2000-09-01
影响因子：
9.6
通讯作者：
Leaper, DJ
中科院分区：
文献类型：
--
作者：
Baker, EA;Bergin, FG;Leaper, DJ
背景：基质金属蛋白酶(MMPs)及其组织抑制物(TIMPs)在肿瘤侵袭转移中起重要作用。方法：采用明胶酶谱(MMP2、MMP9)、酶联免疫吸附试验(MMP1、MMP3、TIMP-1、TIMP-2)和猝灭荧光底物水解法(TMP2、TIMP-1、TIMP-2)检测50例结直肠癌、4例腺瘤和46例结直肠癌手术切除标本中MMPs、TIMP-1和TIMP-2的表达。MMP3和TIMP-1在肿瘤组织中的表达显著高于正常结肠组织(例如TIMP-1肿瘤组织中位数72(范围25-351)和正常组织26(4-107)ng/mg总蛋白含量；然而，正常组织中TIMP-2的水平显著高于正常组织(P<；0.05)。肿瘤组织中总的基质金属蛋白酶活性显著高于正常组织(15025(1750-17400)比7250(750-354650)pmo1 L(-1)分钟(-1)mg蛋白(-1)；P<；0.05)。MMPs和TIMP水平与肿瘤病理分期相关。MMP1的表达与Dukes分期、肿瘤分化程度、淋巴侵袭呈正相关。结论：结直肠癌组织中MMPs水平和总MMPs活性均上调。基质金属蛋白酶-1在结直肠癌的发生发展中起重要作用。
Background: Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) are important in tumour invasion and metastasis. The levels of MMPs, TIMPs and total MMP activity were compared in paired colorectal tumour (n = 50) and normal tissue (n = 49) samples and correlated with clinical and pathological staging.Methods: Gelatin zymography (MMP-2 and MMP-9), enzyme-linked immunosorbent assays (MMP-1, MMP-3, TIMP-1 and TIMP-2) and quenched fluorescent substrate hydrolysis (total MMP activity) were employed in resection specimens from 50 patients, four with adenomas and 46 with colorectal cancer.Results: The levels of active MMP-2 and MMP-9 and total MMP-1, MMP-3 and TIMP-1 were significantly greater in tumour tissue than in normal colon (e.g. TIMP-1 tumour median 72 (range 25-351) versus normal 26 (4-107) ng per mg total protein content; P < 0.05); however, TIMP-2 levels were significantly greater in normal tissue (P < 0.05). Total MMP activity was significantly greater in tumour than in normal tissue (15 025 (1750-174 400) versus 7250 (750-354 650) pmol l(-1) min(-1) mg protein(-1) ; P < 0.05). Correlations were found between both MMP and TIMP levels and pathological tumour staging. MMP-1 appeared to be most important as its concentration correlated positively with Dukes staging, tumour differentiation and lymphatic invasion.Conclusion: The levels of the studied MMPs and total MMP activity were upregulated in colorectal tumours. MMP-1 is important in colorectal cancer progression.