Differential matrix metalloproteinase levels in adenocarcinoma and squamous cell carcinoma of the lung

Abstract

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.