Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases which hydrolyze components of the extracellular matrix (ECM). Physiologically, these enzymes play a pivotal role in normal tissue re-modeling events such as in embryonic development, angiogenesis, ovulation, mammary gland involution and wound healing. Moreover, high expression MMPs has been linked to several pathologies, including cancer invasiveness. Evidence from many clinical studies prompts further investigation of the pathophysiologic role of MMP-1 in metastatic progression. Increased MMP-1 expression has been associated with the incidence or invasiveness of various types of cancer, including colorectal, esophageal, pancreatic, gastric, breast, and malignant melanoma. Furthermore, elevated MMP-1 expression in atypical ductal hyperplastic tissues may serve as a marker for predicting which patients will develop invasive breast cancer. In addition to functions in tissue remodeling, tumor progression, and metastasis through its proteolytic activities for extracellular matrix (ECM) degradation, invasion, and cytokine mobilization, MMP-1 may also promote tumor invasion through proteolytic activation of the G protein coupled receptor PAR1. MMP-1 has also been shown to liberate signaling molecule precursors, such as pro-TGFα, other EGF-like ligands and TGFβ from cell surfaces or matrix. This function may act to drive autocrine or paracrine signaling within the tissue environment, such that MMP-1 can contribute to angiogenesis or osteoclast activation.
Liu H, et al. The role of MMP-1 in breast cancer growth and metastasis to the brain in a xenograft model. BMC Cancer. 2012;12:583.