Metalloproteinases: role in breast carcinogenesis, invasion and metastasis

The matrix metalloproteinases (MMPs) are a family of zinc-dependent endopep tidases. Their primary function is degradation of proteins in the extracell ular matrix. Currently, at least 19 members of this family are known to exi st. Based on substrate specificity and domain organization, the MMPs can be loosely divided into four main groups: the interstitial collagenases, gela tinases, stromelysins and membrane-type MMPs. Recent data from model system s suggest that MMPs are involved in breast cancer initiation, invasion and metastasis. Consistent with their role in breast cancer progression, high l evels of at least two MMPs (MMP-2 and stromelysin-3) have been found to cor relate with poor prognosis in patients with breast cancer. Because MMPs are apparently involved in breast cancer initiation and dissemination, inhibit ion of these proteinases may be of value both in preventing breast cancer a nd in blocking metastasis of established tumours.