Differences in Plasma MMPs and TIMPs Protein Expression and Chemotherapy Response in Patients with Tobacco- or Wood-Smoke-Induced Lung Cancer

Abstract

Background: One of the risk factors associated with lung cancer in never-smoker patients is wood smoke exposure (WS). However, information about its clinical and molecular characteristics remains scant. Objective: This was to analyze - in plasma from patients with tobacco- or wood-smoke-induced lung cancer - whether the enzymatic activity and concentration of matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) differ, and to determine whether there was a correlation between these indicators of the metastatic potential and the first-line chemotherapy response. Methods: Patients were classified according to lung cancer associated with: the smoking of tobacco (T), WS and where no association with a known risk factor (N) could be established. The gelatinase activity of plasma MMP was analyzed by radiolabeled substrate degradation and zymography assay. Protein expression of MMPs and TIMPs was evaluated by Western blot densitometry analysis. Results: The 26.9% WS patients had a better response to therapy in comparison with the T group (OR = 4.9, 95% CI = 1.25-20.15; p = 0.019). The lowest gelatinase activity was observed in WS subjects, in comparison with T and N subjects (96.7 ± 15.9, 182.9 ± 31.5 and 163.3 ± 22.7 µg of degraded gelatin/mg of incubated plasma protein, respectively; p < 0.025); this enzymatic activity corresponded to MMP-2. The highest MMP-2, MMP-9, MT1-MMP and TIMP-1 plasma levels were observed in T subjects. Conclusion: Tobacco and wood smoke have different effects on MMP and TIMP synthesis and gelatinase activity, directly influencing lung cancer metastatic potential and chemotherapy response.