Association of expression of metalloproteinases and their inhibitors with the metastatic potential of squamous-cell lung carcinomas - A molecular and immunohistochemical study
Association of expression of metalloproteinases and their inhibitors with the metastatic potential of squamous-cell lung carcinomas - A molecular and immunohistochemical study
复制标题
DOI：
10.1164/ajrccm.156.6.9612046
复制
发表时间：
1997-12-01
影响因子：
24.7
通讯作者：
Bouros, D
中科院分区：
文献类型：
--
作者：
Karameris, A;Panagou, P;Bouros, D
基质金属蛋白酶（MP）是一个蛋白水解酶（蛋白酶）家族，可降解细胞外基质（ECM）并促进癌细胞的局部或转移潜力，其作用受到特殊抑制剂（金属蛋白酶抑制剂；MI）的抑制。我们评估了 MPs stromelysin-3 (STR-3)、假定的金属蛋白酶-1 (PUMP-1) 和分子量 72 kDa 和 92 kDa 的明胶酶的作用，以及它们的抑制剂金属蛋白酶-1 (TIMP-1) 和 TIMP-2 的组织抑制剂作为 25 个鳞状细胞肺新鲜活检中转移潜能标志物的作用 癌（SCLC）。我们通过Northern印迹分析检测了10例无淋巴结受累的高中分化癌和15例有淋巴结受累的中低分化浸润癌中这些MP和抑制剂的信使核糖核酸（mRNA）表达水平，并以5例上皮显着异型性和5例正常粘膜样本作为对照。 STR-3 和 TIMP-2 的表达也用抗生物素蛋白-生物素复合物 (ABC) 技术进行免疫组织化学评估。我们注意到，从上皮异型性阶段到检测到癌，MPs，尤其是STR-3和TIMP-2的表达水平逐渐增加，发现这些物质在伴有淋巴结转移的低分化癌中最高。这些发现也通过免疫组织化学分析得到证实。我们的结果表明，MP 和 MI 的表达与 SCLC 的局部和转移潜力以及细胞分化程度存在显着相关性，并且这种相关性因其预后和治疗意义而具有临床重要意义。
Matrix metalloproteinases (MPs) constitute a family of proteolytic enzymes (proteases) that degrade extracellular matrix (ECM) and promote the local or metastatic potential of carcinoma cells, and whose action is restrained by special inhibitors (metalloproteinase inhibitors; MIs). We assessed the role of the MPs stromelysin-3 (STR-3), putative metalloproteinase-1 (PUMP-1), and the gelatinases of molecular weights 72 kDa and 92 kDa, as well as the role of their inhibitors tissue inhibitor of metalloproteinase-1 (TIMP-1) and TIMP-2, as markers of metastatic potential in 25 fresh biopsies of squamous-cell lung carcinomas (SCLCs). We examined levels of messenger ribonucleic acid (mRNA) expression for these MPs and inhibitors through Northern blot analysis in 10 carcinomas of high-to-moderate differentiation without lymph-node involvement, and in 15 infiltrative carcinomas of moderate-to-low differentiation with lymph-node involvement, Five cases with significant epithelial atypia and five samples with normal mucosa were used as controls. Expression of STR-3 and TIMP-2 was also assessed immunohistochemically with the avidin-biotin-complex (ABC) technique. We noticed a progressive increase in the expression levels of MPs, especially of STR-3, and of TIMP-2, from the stage of epithelial atypia to the detection of carcinoma, finding the highest values of these substances among carcinomas of low differentiation with nodal metastases. These findings were also confirmed with immunohistochemical analysis. Our results suggest that there is a significant association of the expression of MPs and MIs with both the local and metastatic potential and the degree of cellular differentiation of SCLC, and that this association is clinically important because of its prognostic and therapeutic implications.