Kubben Frank J G M, Sier Cornelis F M, Hawinkels Lukas J A C, Tschesche Harald, van Duijn Wim, Zuidwijk Kim, van der Reijden Johan J, Hanemaaijer Roeland, Griffioen Gerrit, Lamers Cornelis B H W, Verspaget Hein W
Department of Gastroenterology - Hepatology, Leiden University Medical Centre, P.O. Box 9600, 2300 RC Leiden, The Netherlands.
Eur J Cancer. 2007 Aug;43(12):1869-76. doi: 10.1016/j.ejca.2007.05.013. Epub 2007 Jul 2.
Recently, complexes of matrix metalloproteinase matrix metalloproteinase-9 (MMP-9) with lipocalin-2 (neutrophil gelatinase-associated lipocalin) were found in the urine obtained from breast cancer patients, while these were completely absent in that obtained from healthy controls. In vitro data suggested a possible role for lipocalin-2 in the protection of MMP-9 against autolysis. To establish this effect in vivo, we determined the presence of MMP-9, lipocalin-2 and their complex in tumour tissue from 81 gastric cancer patients. The effect of the presence of the individual parameters, the complexes, and the inhibitors TIMP-1 and TIMP-2 on MMP-9 activity was evaluated with a bioactivity assay. Immuno-histochemical (double) staining identified epithelial cells as the most likely cellular source. Finally, evaluation of all these parameters with clinico-pathological scores revealed that tumour MMP-9/lipocalin-2 complexes were significantly related with the classifications of Laurén and WHO, and highly associated with worse survival in Cox's univariate (HR 2.087, P=0.006) and multivariate analyses (HR 2.095, P=0.025).
最近，在乳腺癌患者的尿液中发现了基质金属蛋白酶-9（MMP-9）与脂质运载蛋白-2（中性粒细胞明胶酶相关脂质运载蛋白）的复合物，而在健康对照者的尿液中则完全没有。体外数据表明脂质运载蛋白-2可能在保护MMP-9免受自溶方面发挥作用。为了在体内证实这种作用，我们检测了81例胃癌患者肿瘤组织中MMP-9、脂质运载蛋白-2及其复合物的存在情况。通过生物活性测定评估了各个参数、复合物以及抑制剂TIMP-1和TIMP-2的存在对MMP-9活性的影响。免疫组织化学（双重）染色确定上皮细胞是最可能的细胞来源。最后，用临床病理评分对所有这些参数进行评估，结果显示肿瘤MMP-9/脂质运载蛋白-2复合物与Laurén分类和世界卫生组织分类显著相关，并且在Cox单因素分析（风险比2.087，P = 0.006）和多因素分析（风险比2.095，P = 0.025）中与较差的生存率高度相关。
