Gill Jason H, Kirwan Ian G, Seargent Jill M, Martin Sandie W, Tijani Sidiq, Anikin Vladimir A, Mearns Alan J, Bibby Michael C, Anthoney Alan, Loadman Paul M
Cancer Research UK Laboratories, Tom Connors Cancer Research Centre, University of Bradford, Bradford BD7 1DP, UK.
Neoplasia. 2004 Nov-Dec;6(6):777-85. doi: 10.1593/neo.04283.
Matrix metalloproteinase (MMP)-mediated degradation of the extracellular matrix is a major factor for tumor development and expansion. This study analysed MMP-10 protein expression and activity in human lung tumors of various grade, stage, and type to address the relationship between MMP-10 and tumor characteristics and to evaluate MMP-10 as a therapeutic target in non small cell lung carcinoma (NSCLC). Unlike the majority of MMPs, MMP-10 was located in the tumor mass as opposed to tumor stroma. MMP-10 protein was observed at low levels in normal human lung tissues and at significantly higher levels in all types of NSCLC. No correlation was observed between MMP-10 protein expression and tumor type, stage, or lymph node invasion. To discriminate between active and inactive forms of MMP-10 in samples of human NSCLC, we have developed an ex vivo fluorescent assay. Measurable MMP-10 activity was detected in 42 of 50 specimens of lung cancer and only 2 of 10 specimens of histologically normal lung tissue. No relationship was observed between MMP-10 activity levels and clinicopathologic characteristics. Our results suggest that MMP-10 is expressed and active at high levels in human NSCLC compared to normal lung tissues, and, as such, is a potential target for the development of novel therapeutics for lung cancer treatment.
基质金属蛋白酶（MMP）介导的细胞外基质降解是肿瘤发生和发展的主要因素。本研究分析了不同分级、分期和类型的人类肺肿瘤中MMP-10蛋白的表达和活性，以探讨MMP-10与肿瘤特征之间的关系，并评估MMP-10作为非小细胞肺癌（NSCLC）治疗靶点的可能性。与大多数MMP不同，MMP-10位于肿瘤块中而非肿瘤基质中。在正常人类肺组织中观察到MMP-10蛋白水平较低，而在所有类型的NSCLC中其水平显著更高。未观察到MMP-10蛋白表达与肿瘤类型、分期或淋巴结浸润之间存在相关性。为了区分人类NSCLC样本中MMP-10的活性形式和非活性形式，我们开发了一种体外荧光测定法。在50份肺癌标本中的42份以及10份组织学正常的肺组织标本中的2份中检测到了可测量的MMP-10活性。未观察到MMP-10活性水平与临床病理特征之间存在关系。我们的结果表明，与正常肺组织相比，MMP-10在人类NSCLC中高水平表达且具有活性，因此，它是开发肺癌治疗新疗法的潜在靶点。
