Estrogenic control of matrix metalloproteinases: a perspective on breast tumor invasion and metastasis.

Abstract

Metastasis is the major cause of mortality in breast cancer patients, and presents an invincible therapeutic challenge. It is a complex process of dissemination of tumor epithelial cells, which is associated with disruption of tissue homeostasis, and alterations in the tumor microenvironment through extracellular matrix (ECM) remodeling, stromal alteration, and epithelial-mesenchymal transition. Matrix metalloproteinases (MMPs) constitute a group of more than 25 zinc-dependent endopeptidases. By virtue of their ability to degrade a wide variety of ECM-associated proteins, they enable ECM remodelling during development, and disease. A large body of clinical data, and experimental evidences implicate MMPs in the invasion and metastasis of breast tumors. While MMPs are aberrantly expressed in breast tumors, few appear to have a dual role in disease progression; either promoting or inhibiting metastasis. Given the role of estrogen in breast cancer development, it is natural to ask whether this steroid hormone has any role in breast cancer metastasis. This review is a round-up of the prominent literature that presents estrogenic control of MMPs, which in turn implies its influence on the tumor microenvironment and metastasis.