An overview of collagenase-3 expression in malignant tumors and analysis of its potential value as a target in antitumor therapies

Collagenase-3 (MMP-13) is a member of the matrix metalloproteinase family o f endopeptidases that is characterized by a potent degrading activity again st a wide spectrum of substrates. This enzyme was first detected in breast carcinomas but it is also overexpressed in a variety of malignant tumors in cluding head and neck carcinomas, chondrosarcomas, skin carcinomas, and car cinomas of the female genital tract. Clinical studies have revealed that in all these tumors collagenase-3 expression is associated with invasive and metastatic tumors. Analysis of the molecular mechanisms underlying its mark ed overexpression in malignant tumors has allowed to identify different cyt okines, growth factors and tumor promoters with ability to up-regulate coll agenase-3 expression in tumor cells, or in stromal fibroblasts surrounding epithelial tumor cells. The first strategies designed to target this enzyme are being developed, and are mainly directed to prepare synthetic inhibito rs with ability to selectively block the collagenase-3 proteolytic activity . Alternatively, inhibitors of the signal transduction pathways mediating t he expression of this enzyme by tumor cells may also be useful for collagen ase-3 targeting. These studies together with those performed on other enzym es associated with tumor processes may lead to the development of novel the rapeutic strategies to control the progression and metastatic capacity of n eoplastic cells. (C) 2000 Elsevier Science B.V. All rights reserved.