Balance between activation and inhibition of matrix metalloproteinase-2 (MMP-2) is altered in colorectal tumors compared to normal colonic epithelium.
Balance between activation and inhibition of matrix metalloproteinase-2 (MMP-2) is altered in colorectal tumors compared to normal colonic epithelium.
复制标题
与正常结肠上皮相比，结直肠肿瘤中基质金属蛋白酶 2 (MMP-2) 的激活和抑制之间的平衡发生了改变。
DOI：
10.1023/a:1016456914723
复制
发表时间：
2002
影响因子：
3.1
通讯作者：
Cohn,KennethH
中科院分区：
文献类型：
--
作者：
Ornstein,DeborahL;Cohn,KennethH
基质金属蛋白酶-2 (MMP-2) 在人类癌症中过度表达，促进肿瘤生长和转移。它被合成为无活性酶原，被膜型基质金属蛋白酶-1 (MT1-MMP) 激活并被金属蛋白酶-2 组织抑制剂 (TIMP-2) 抑制。我们假设，与正常结肠组织相比，恶性结肠肿瘤中 TIMP-2 的表达与 MMP-2 和 MT1-MMP 的表达之间存在不平衡，有利于 MMP-2 的激活。在手术切除时，从 22 名患者身上获取了结肠肿瘤和邻近正常粘膜的样本。使用定量逆转录酶聚合酶链反应测定法测量每个样品中的 MMP-2、MT1-MMP 和 TIMP-2 RNA 转录物。我们观察到，与正常组织相比，肿瘤中 MMP-2 RNA 水平显着升高（P = 0.039）。此外，与正常粘膜相比，肿瘤中的TIMP-2:MMP-2比率低两倍(P = 0.001)，TIMP-2:MT1-MMP比率低1.5倍(P = 0.003)。这些结果表明，在结肠肿瘤中，激活和抑制 MMP-2 的基因之间的平衡转向激活。调节MMP-2活性的基因产物的异常表达可能是结肠癌恶性转化的重要早期步骤，并可能为新的化学预防和辅助治疗策略提供有用的靶点。
Matrix metalloproteinase-2 (MMP-2) is overexpressed in human cancers and facilitates tumor growth and metastasis. It is synthesized as an inactive proenzyme that is activated by membrane-type matrix metalloproteinase-1 (MT1-MMP) and inhibited by tissue inhibitor of metalloproteinase-2 (TIMP-2). We hypothesized that there is an imbalance between the expression of TIMP-2 and the expression of MMP-2 and MT1-MMP that favors activation of MMP-2 in malignant colon tumors compared to normal colonic tissue. Specimens of colon tumors and of adjacent normal mucosa were obtained from 22 patients at the time of surgical resection. MMP-2, MT1-MMP, and TIMP-2 RNA transcripts were measured in each sample using a quantitative reverse transcriptase polymerase chain reaction assay. We observed that MMP-2 RNA levels were significantly elevated in tumors compared to normal tissue(P = 0.039). In addition, the TIMP-2:MMP-2 ratio was twofold lower (P = 0.001)and the TIMP-2:MT1-MMP ratio was 1.5-fold lower(P = 0.003)in tumors compared to normal mucosa. These results suggest that the balance between genes that activate and inhibit MMP-2 is shifted toward activation in colon tumors. The abnormal expression of gene products that regulate MMP-2 activity may be an important early step in the malignant transformation of colon cancer and may provide a useful target for new chemoprevention and adjuvant treatment strategies.