Characterization of a novel metalloproteinase in tissue repair, inflammation and cancer

Matrix metalloproteinases (MMPs) is a family of more than 20 enzymes that take part in the degradation of extracellular matrix and basement membranes during cell migration, angiogenesis and proteolytic activation of growth factors. These events are needed in fetal development and in normal tissue remodelling as well as in epidermal wound healing, inflammation and tumour invasion.

Our group has recently cloned a new member of this group, human matrix metalloproteinase-21 (MMP-21), which has been suggested to play an important role in embryogenesis and tumour progression. It is expressed in a variety of fetal and adult normal tissues, as well as in some tumour tissues and tumour cell lines, including breast, ovary, lung and prostate carcinomas, epidermoid carcinomas and osteosarcomas. Not much is known about the regulation of this gene, but it has been shown that transforming growth factor (TGF)-beta1 induces the transcription of the MMP-21 gene in HaCaT keratinocyte cell line. Further, it has been suggested that MMP-21 is a target of the Wnt, Pax and Notch signalling pathways.

Our primary interest is to study how this gene is expressed in cell types important for tissue repair, inflammation and cancer. Further, we will study the regulation of gene expression, and the activation and substrates of the MMP-21 gene.

Methods we will use are cell culturing, transient and stable transfections, RT-PCR, TaqMan, Western, immunohistochemistry, and expression and purification of recombinant proteins in different cell types.