1. ¹Laboratory of Pneumology and Laboratory of Tumor and Development Biology, Center for Biomedical Integrative Genoproteomics (CBIG), University of Liège and Centre Hospitalier Universitaire de Liège (CHU-Liège), Avenue de l'Hôpital, CHU, Sart-Tilman, Liège 4000, Belgium
2. ²INSERM U514, Laboratory Pol Bouin, Hôpital Maison Blanche CHU, Reims, France

Correspondence: Dr D Cataldo, E-mail: Didier.Cataldo@ulg.ac.be

Received 19 September 2005; Revised 21 December 2005; Accepted 17 January 2006; Published online 21 February 2006.

Abstract

A Disintegrin and Metalloprotease (ADAM) are transmembrane proteases displaying multiple functions. ADAM with ThromboSpondin-like motifs (ADAMTS) are secreted proteases characterised by thrombospondin (TS) motifs in their C-terminal domain. The aim of this work was to evaluate the expression pattern of ADAMs and ADAMTS in non small cell lung carcinomas (NSCLC) and to investigate the possible correlation between their expression and cancer progression. Reverse transcriptase–polymerase chain reaction (RT–PCR), Western blot and immunohistochemical analyses were performed on NSCLC samples and corresponding nondiseased tissue fragments. Among the ADAMs evaluated (ADAM-8, -9, -10, -12, -15, -17, ADAMTS-1, TS-2 and TS-12), a modulation of ADAM-12 and ADAMTS-1 mRNA expression was observed. Amounts of ADAM-12 mRNA transcripts were increased in tumour tissues as compared to the corresponding controls. In sharp contrast, ADAMTS-1 mRNA levels were significantly lower in tumour tissues when compared to corresponding nondiseased lung. These results were corroborated at the protein level by Western blot and immunohistochemistry. A positive correlation was observed between the mRNA levels of ADAM-12 and those of two vascular endothelial growth factor (VEGF)-A isoforms (VEGF-A₁₆₅ and VEGF-A₁₂₁). Taken together, these results providing evidence for an overexpression of ADAM-12 and a lower expression of ADAMTS-1 in non-small-cell lung cancer suggest that these proteases play different functions in cancer progression.