PURPOSE: Non-small cell lung cancer (NSCLC) is a very common and aggressive malignancy. Survival after resection of tumor is especially determined by the occurrence of distant metastasis. Matrix metalloproteinases (MMP) support this metastatic process by degradation of the extracellular matrix. EXPERIMENTAL DESIGN: We used DNA microarray technology to examine the expression of 22 MMPs in 89 surgically treated NSCLC patients. Validation of microarray results was done using reverse transcription-PCR and immunohistology. RESULTS: MMP-1, MMP-9, and MMP-12 expression was significantly increased in tumors versus corresponding lung tissues. MMP-12 expression significantly correlated with local recurrence and metastatic disease. Multivariate Cox regression analysis revealed MMP-12 expression as an independent prognostic factor for tumor relapse-free interval. Gene expression analysis of 158 healthy tissues from 32 different organs revealed no MMP-12 expression in these organs and immunohistology identified MMP-12 protein in NSCLC only in tumor cells. CONCLUSIONS: MMP-12 might be not only a prognostic marker, but also a valuable therapeutic target.
PURPOSE:Non-small cell lung cancer (NSCLC) is a very common and aggressive malignancy. Survival after resection of tumor is especially determined by the occurrence of distant metastasis. Matrix metalloproteinases (MMP) support this metastatic process by degradation of the extracellular matrix. EXPERIMENTAL DESIGN: We used DNA microarray technology to examine the expression of 22 MMPs in 89 surgically treated NSCLCpatients. Validation of microarray results was done using reverse transcription-PCR and immunohistology. RESULTS:MMP-1, MMP-9, and MMP-12 expression was significantly increased in tumors versus corresponding lung tissues. MMP-12 expression significantly correlated with local recurrence and metastatic disease. Multivariate Cox regression analysis revealed MMP-12 expression as an independent prognostic factor for tumor relapse-free interval. Gene expression analysis of 158 healthy tissues from 32 different organs revealed no MMP-12 expression in these organs and immunohistology identified MMP-12 protein in NSCLC only in tumor cells. CONCLUSIONS:MMP-12 might be not only a prognostic marker, but also a valuable therapeutic target.
Authors: Arun R Pandiri; Robert C Sills; Vincent Ziglioli; Thai-Vu T Ton; Hue-Hua L Hong; Stephanie A Lahousse; Kevin E Gerrish; Scott S Auerbach; Keith R Shockley; Pierre R Bushel; Shyamal D Peddada; Mark J Hoenerhoff Journal: Toxicol Pathol Date: 2012-06-11 Impact factor: 1.902
Authors: Cesar E Ochoa; Seyedeh Golsar Mirabolfathinejad; Venado Ana Ruiz; Scott E Evans; Mihai Gagea; Christopher M Evans; Burton F Dickey; Seyed Javad Moghaddam Journal: Cancer Prev Res (Phila) Date: 2010-11-22
Authors: Joanna L Richens; Richard A Urbanowicz; Elizabeth A M Lunt; Rebecca Metcalf; Jonathan Corne; Lucy Fairclough; Paul O'Shea Journal: Respir Res Date: 2009-04-22
Authors: Günther H S Richter; Stephanie Plehm; Annette Fasan; Sabine Rössler; Rebekka Unland; Idriss M Bennani-Baiti; Marc Hotfilder; Diana Löwel; Irene von Luettichau; Ilona Mossbrugger; Leticia Quintanilla-Martinez; Heinrich Kovar; Martin S Staege; Carsten Müller-Tidow; Stefan Burdach Journal: Proc Natl Acad Sci U S A Date: 2009-03-16 Impact factor: 11.205
Authors: Mark J Cartwright; Karen Schlauch; Marc E Lenburg; Tamara Tchkonia; Tamar Pirtskhalava; Andrew Cartwright; Thomas Thomou; James L Kirkland Journal: J Gerontol A Biol Sci Med Sci Date: 2010-01-27 Impact factor: 6.053