Somiari Stella B, Shriver Craig D, Heckman Caroline, Olsen Cara, Hu Hai, Jordan Rick, Arciero Cletus, Russell Stephen, Garguilo Gerald, Hooke Jeffrey, Somiari Richard I
Clinical Breast Care Project, Windber Research Institute, 600 Somerset Avenue, Windber, PA 15963, USA.
Cancer Lett. 2006 Feb 20;233(1):98-107. doi: 10.1016/j.canlet.2005.03.003.
Matrix metalloproteinases (MMPs) are involved in extracellular matrix modification and associated with invasive and metastatic behavior of human malignant tumors. Specifically, MMP2 and MMP9 are implicated in both early and late processes of tumor development. It is reported that MMPs occur as inactive precursors, active enzymes or enzyme inhibitor complexes in biological samples. However, there is limited knowledge on the role of each form in disease and/or the significance of changes in the plasma concentration and/or activity in breast cancer patients. The aim of this study was to determine if patients with breast cancer, benign disease and at risk for developing breast cancer display characteristic levels of active and/or total MMP2 and MMP9 in plasma. Concentration and activity of MMP2 and MMP9 were determined quantitatively in the plasma of 124 female volunteers diagnosed with breast cancer (n=31), benign disease (n=38), or determined by the Gail Model to be at high risk (n=31) or low risk (controls, n=24) of developing breast cancer. Data obtained was statistically analyzed to search for differences/patterns characteristic of each category. Concentration of total MMP2 was significantly lower in control individuals than benign, high risk (P<0.001 respectively) and breast cancer patients (P=0.002). Activity of total MMP2 was significantly lower in controls compared to cancer, benign and high risk patients (P<0.001 respectively). Attempts to build a predictive/descriptive model using canonical discriminant analysis (utilizing all eight features; concentrations and activity levels of active/total MMP2 and MMP9) enabled the distinction of the controls from the high risk, benign and cancer groups. Our results suggest that preoperative plasma concentration and activity of MMP2 and MMP9 may permit sub-classification of female patients with breast disorders.
基质金属蛋白酶（MMPs）参与细胞外基质的修饰，并与人类恶性肿瘤的侵袭和转移行为相关。具体而言，MMP2和MMP9与肿瘤发展的早期和晚期过程均有关联。据报道，MMPs在生物样本中以无活性前体、活性酶或酶抑制剂复合物的形式存在。然而，关于每种形式在疾病中的作用以及乳腺癌患者血浆浓度和/或活性变化的意义，人们了解有限。本研究的目的是确定患有乳腺癌、良性疾病以及有患乳腺癌风险的患者血浆中活性和/或总MMP2及MMP9是否呈现特征性水平。对124名女性志愿者的血浆进行定量测定，这些志愿者被诊断为患有乳腺癌（n = 31）、良性疾病（n = 38），或根据盖尔模型确定为患乳腺癌的高风险（n = 31）或低风险（对照组，n = 24）人群。对获得的数据进行统计分析，以寻找各类别的差异/特征模式。对照组个体中总MMP2的浓度显著低于良性疾病患者、高风险患者（P值分别<0.001）和乳腺癌患者（P = 0.002）。与癌症患者、良性疾病患者和高风险患者相比，对照组中总MMP2的活性显著较低（P值分别<0.001）。尝试使用典型判别分析构建预测/描述模型（利用所有八个特征；活性/总MMP2和MMP9的浓度及活性水平）能够区分对照组与高风险组、良性疾病组和癌症组。我们的结果表明，术前血浆中MMP2和MMP9的浓度及活性可能有助于对患有乳腺疾病的女性患者进行亚分类。
