Collagenases in cancer

Abstract

Three mammalian collagenases (MMP-1, MMP-8, and MMP-13) belong to family of matrix metalloproteinases and are the principal secreted endopeptidases capable of cleaving collagenous extracellular matrix. In addition to fibrillar collagens, collagenases can cleave several other matrix and non-matrix proteins including growth factors, and this way regulate cell growth and survival. Collagenases are important proteolytic tools for extracellular matrix remodeling during organ development and tissue regeneration, but they also apparently play important roles in many pathological situations and tumor progression and metastasis. Because of their potentially destructive characteristics the expression and activity of collagenases are strictly controlled. Synthesis of collagenases is regulated by extracellular signals via cellular signal transduction pathways at transcriptional and post-transcriptional level. Collagenases are synthesized as inactive pro-forms, and once activated, their activity is inhibited by specific tissue inhibitors of metalloproteinases, TIMPs, as well as by non-specific proteinase inhibitors. In this review we discuss the current view on the role of collagenases in tumor growth, invasion, and metastasis, as a basis for their feasibility in diagnosis and prognostication, as well as therapeutic targets in cancer patients.