Matrix metalloproteinases 15 and 19 are stromal regulators of colorectal cancer development from the early stages

Matrix metalloproteinases (MMPs) have been well characterized for theirability to degrade extracellular matrix proteins and, thus, they have been studiedto elucidate their involvement in both tumor development and progression. In thepresent study, attention was focused on MMP-15 and MMP-19, two less known membersof the MMP family. The expression profile of MMP-15 and -19 was assayed in samplesof normal colorectal mucosa, microadenomas and cancer using confocal analysis,western blotting and quantitative reverse transcription polymerase chain reaction(qRT-PCR). Both qRT-PCR and western blotting showed that MMP-15 and MMP-19 appearedto be upregulated during colorectal tumorigenesis, with different expression patterns:MMP-15 expression level increases from normal mucosa to microadenomas, with areduced level in cancer with respect to microadenomas; the semiquantitative immunofluorescenceanalysis showed a stromal localization of this protein in the early phases ofneoplastic transformation. Increasing amount of MMP-19 mRNA and protein levelswere observed in the progression of colonic lesions; MMP-19 staining increasedin the normal mucosa-microadenoma-carcinoma sequence. Such different expressionpatterns, are probably due to the different roles played in colorectal tumorigenesisby these two molecules. Conflicting data on the role of these proteins in tumorprogression have been reported, thus, an improved understanding of the biologicalroles of MMPs, in particular the lesser known members such as MMP-15 and 19, incolorectal cancer may lead to a re-evaluation of the use of MMP inhibitors andsuggests the need of integrated translational studies on MMP expression patterns.