Fax +41 61 306 12 34 E-Mail karger@karger.com www.karger.com Clinical Investigations Respiration 2013;85:281–288 DOI: 10.1159/000336559 Differences in Plasma MMPs and TIMPs Protein Expression and Chemotherapy Response in Patients with Tobacco- or Wood-Smoke-Induced Lung Cancer Georgina Gonzalez-Avila Javier Delgado Daniel A. Mendoza-Posada Bettina Sommer Carlos Ramos Arnoldo Aquino-Galvez Catalina Camacho Laboratorio de Oncología Biomédica, Departamento de Enfermedades Crónico Degenerativas, Instituto Nacional de Enfermedades Respiratorias ‘Ismael Cosio Villegas’, México, México 1.25–20.15; p = 0.019). The lowest gelatinase activity was ob- served in WS subjects, in comparison with T and N subjects (96.7 8 15.9, 182.9 8 31.5 and 163.3 8 22.7 g 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 meta- static potential and chemotherapy response. Copyright © 2012 S. Karger AG, Basel Introduction Tobacco has been considered the main risk factor in lung cancer pathogenesis. However, statistics show that 15% of men and 53% of women with lung cancer are nev- er-smokers [1]. In recent years, epidemiological studies have identified several etiological factors that could be involved in lung cancer onset in never-smokers, such as exposure to radon, coal smoke, wood smoke or asbestos, as well as genetic, hormonal and viral factors [2, 3]. In developing countries, wood, dung and charcoal (de- fined as ‘biomass fuel’) are burned and used as low-cost fuel sources for cooking, heating and lighting [4]. The use Key Words Gelatinase activity  Lung cancer  Matrix metalloproteinases  Never-smokers  Tissue inhibitors of matrix metalloproteinases  Wood smoke 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 molec- ular 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 to- bacco (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 degra- dation and zymography assay. Protein expression of MMPs and TIMPs was evaluated by Western blot densitometry anal- ysis. Results: The 26.9% WS patients had a better response to therapy in comparison with the T group (OR = 4.9, 95% CI = Received: August 27, 2011 Accepted after revision: January 10, 2012 Published online: March 22, 2012 Georgina González-Avila, MD, PhD, Laboratorio de Oncología Biomédica Departamento de Enfermedades Crónico Degenerativas Instituto Nacional de Enfermedades Respiratorias ‘Ismael Cosio Villegas Calzada de Tlalpan 4502, CP 14080, México, D.F. (México) Tel. +52 55 5487 1700, ext. 5287, E-Mail ggonzalezavila  @  yahoo.com © 2012 S. Karger AG, Basel 0025–7931/13/0854–0281$38.00/0 Accessible online at: www.karger.com/res