title: 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.
  
  
  CONCLUSIONS
  Tobacco and wood smoke have different effects on MMP and TIMP synthesis and gelatinase activity, directly influencing lung cancer metastatic potential and chemotherapy response.
authors.affiliation: Laboratorio de Oncología Biomédica, Departamento de Enfermedades Crónico Degenerativas, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas, México. ggonzalezavila @ yahoo.com
authors.forename: Georgina
authors.initials: G
authors.lastname: Gonzalez-Avila
authors.forename: Javier
authors.initials: J
authors.lastname: Delgado
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Mendoza-Posada
authors.forename: Bettina
authors.initials: B
authors.lastname: Sommer
authors.forename: Carlos
authors.initials: C
authors.lastname: Ramos
authors.forename: Arnoldo
authors.initials: A
authors.lastname: Aquino-Galvez
authors.forename: Catalina
authors.initials: C
authors.lastname: Camacho
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000201:enzymology* / Q000209:etiology; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000209:etiology; D008297:Male; D020782:Matrix Metalloproteinases / Q000097:blood*; D008875:Middle Aged; D012307:Risk Factors; D012906:Smoke / Q000009:adverse effects*; D012907:Smoking / Q000009:adverse effects*; D019714:Tissue Inhibitor of Metalloproteinases / Q000097:blood*; D016896:Treatment Outcome; D014934:Wood; D014026:Nicotiana
chemical_list: D000970:Antineoplastic Agents; D012906:Smoke; D019714:Tissue Inhibitor of Metalloproteinases; D020782:Matrix Metalloproteinases