EXPRESSION PROFILES OF MATRIX METALLOPROTEINASES 15 AND 19 IN HUMAN COLORECTAL CARCINOGENESIS

INTRODUCTION: The matrix metalloproteinases (MMPs) have been well characterized for their ability to degrade extracellular matrix proteins and thus they have been extensively studied to elucidate their involvement in both tumour development and progression. In the present study the attention were focused on two members of MMP family, i.e. MMP-15 and MMP-19.METHODS: The expression profile of MMP-15 and 19 were assayed from samples of normal mucosa, microadenomas and cancer using confocal analysis, Western blotting and quantitative reverse transcription polymerase chain reaction (Q-PCR).RESULTS: The semiquantitative immunofluorescence analysis showed that MMP-15 expression level increases from normal mucosa to microadenomas, with a reduced level in cancer respect to microadenomas, while MMP-19 staining increases in normal mucosa-microadenoma-carcinoma sequence.Both Q-PCR and Western blot methods correlate with immunofluorescence behaviour of MMP-15 and 19, showing a significantly higher expression of MMP-15 in microadenomas compared to normal mucosa, and indicating an increasingly amount of MMP-19 levels in the progression of colon lesions.CONCLUSIONS: MMP-15 and 19 appear to be up-regulated during tumorigenesis, with different expression patterns, that are probably due to the different roles played by these two molecules. The literature up to now reported show conflicting data regarding the role of these proteins in tumor progression so that the improved understanding of the biological roles of MMPs in colorectal cancer should lead to a re-evaluation of the use of MMP inhibitors and highlight the importance of integrated translational studies on the MMP expression patterns.