Division of Cardiothoracic Surgery, Medical University of South Carolina and the Ralph H. Johnson VA Medical Center, Charleston, SC, USA.
J Thorac Cardiovasc Surg. 2010 Apr;139(4):984-90; discussion 990. doi: 10.1016/j.jtcvs.2009.12.016.
The matrix metalloproteinases (MMPs) have been implicated in the aggressive course of non-small cell lung cancer (NSCLC). However, there are a large number of MMP subtypes with diverse proteolytic substrates and different induction pathways. This study tested the hypothesis that a differential MMP profile would exist between NSCLC and normal lung and that MMP patterns would differ between NSCLC histologic types.
NSCLC samples and remote normal samples were obtained from patients with stage I or II NSCLC with either squamous cell (n = 22) or adenocarcinoma (n = 19) histologic characteristics. Absolute concentrations for each of the MMP subclasses were determined by a calibrated and validated multiplex suspension array: collagenases (MMP-1, -8, and -13), gelatinases (MMP-2 and -9), lysins (MMP-2 and -7), and elastase (MMP-12).
Overall, MMP levels were significantly increased in NSCLC compared with normal. For example, MMP-1 and MMP-7 increased by approximately 10-fold in NSCLC (P < .05). Moreover, a different MMP portfolio was observed between NSCLC histologic types. For example MMP-1, -8, -9, and -12 increased by more than 4-fold in squamous cell versus adenocarcinoma (P < .05). In those patients who had recurrence within 3 years of resection, 3-fold higher levels of MMP-8 and -9 were observed (P < .05).
Increased levels of a number of MMP types occur with NSCLC, but the MMP profile was distinctly different between histologic types and in those patients with recurrence. These different MMP profiles may be important in the mechanistic basis for the natural history of different NSCLC types, as well as identifying potential prognostic and therapeutic targets.
基质金属蛋白酶（MMPs）已被牵涉到非小细胞肺癌（NSCLC）的侵袭性病程中。然而，存在大量具有不同蛋白水解底物和不同诱导途径的 MMP 亚型。本研究检验了以下假说，即在 NSCLC 和正常肺之间存在不同的 MMP 谱，并且在 NSCLC 组织学类型之间 MMP 模式会有所不同。
从患有 I 期或 II 期具有鳞状细胞（n = 22）或腺癌（n = 19）组织学特征的 NSCLC 患者中获得 NSCLC 样本和远程正常样本。通过校准和验证的多重悬浮阵列确定每种 MMP 亚类的绝对浓度：胶原酶（MMP-1、-8 和 -13）、明胶酶（MMP-2 和 -9）、溶酶体（MMP-2 和 -7）和弹性蛋白酶（MMP-12）。
总体而言，与正常肺相比，NSCLC 中的 MMP 水平显着升高。例如，在 NSCLC 中 MMP-1 和 MMP-7 增加了约 10 倍（P <.05）。此外，在 NSCLC 组织学类型之间观察到不同的 MMP 组合。例如，与腺癌相比，MMP-1、-8、-9 和 -12 在鳞状细胞中增加了 4 倍以上（P <.05）。在切除后 3 年内复发的患者中，观察到 MMP-8 和 -9 的水平升高了 3 倍（P <.05）。
许多 MMP 类型的水平在 NSCLC 中升高，但 MMP 谱在组织学类型之间以及在复发患者中明显不同。这些不同的 MMP 谱可能在不同 NSCLC 类型的自然史的机制基础以及识别潜在的预后和治疗靶标方面非常重要。
