MMP8 (Matrix metalloproteinase 8) is a member of the family of matrix metalloproteinases. It is distinct from the collagenase of skin fibroblasts and synovial cells in substrate specificity and immunologic crossreactivity. MMP8 was mapped to 11q21-q22. MMP8 is an enzyme that degrades fibrillar collagens imparting strength to the fetal membranes, is expressed by leukocytes and chorionic cytotrophoblast cells. The enzyme exhibits 58% homology to human fibroblast collagenase and has the same domain structure. It consists of a 20-residue signal peptide, and an 80-residue propeptide that is lost on autolytic activation by cleavage of an M-L bond. MMP8 was found to possess 57% identity with the deduced protein sequence for fibroblast collagenase with 72% chemical similarity. Matrix metalloproteinases (MMPs) have fundamental roles in tumor progression, but most clinical trials with MMP inhibitors have not shown improvements in individuals with cancer. MMP8 has a paradoxical protective role in cancer and provides a genetic model to evaluate the molecular basis of gender differences in cancer susceptibility.