Physiological roles of matrix metalloproteinases: implications for tumor growth and metastasis

Abstract

Physiological processes involving remodelling of the extracellular matrix, such as wound healing, embryogenesis, angiogenesis, and the female reproductive cycle, require the activity of matrix metalloproteinases (MMPs). This group of proteases degrades basal membranes and connective tissues and plays an essential role in the homeostasis of the extracellular matrix. An imbalance in the expression or activity of MMPs can have important consequences in diseases such as multiple sclerosis, Alzheimer's disease, or the development of cancers. Because of the pathophysiological importance of MMPs, their activity is highly controlled in order to confine them to specific areas. An activation cascade, initiated by the proteolysis of plasminogen, cleaves proMMPs, and every step is controlled by specific activators or inhibitors. MMPs destabilize the organization of the extracellular matrix and influence the development of cancer by contributing to cell migration, tumor cell proliferation, and angiogenesis. Accordingly, these proteases possess an important role in cell-matrix interactions by affecting fundamental processes such as cell differentiation and proliferation. Therefore, the characterization of MMPs involved in specific types and stages of tumors will significantly improve the diagnosis and treatment of these cancers in humans.

Distribution pattern of matrix metalloproteinases 1, 2, 3, and 9, tissue inhibitors of matrix metalloproteinases 1 and 2, and α2-macroglobulin in cases of generalized AA- and AL amyloidosis

“…MMPs play an essential role in the homeostasis of the extracellular matrix and may be involved in tissue remodeling during deposition of amyloid [5]. However, we did not find any MMPs within AL amyloid deposits or any TIMPs within AA amyloid deposits.…”

“…This group of proteases degrades basement membranes and connective tissue and plays an essential role in the homeostasis of the extracellular matrix. An imbalance in the expression and/or activity of MMPs can have important consequences in the development of diseases such as cancer and Alzheimer's disease [4,5,20,32]. The latter is a cerebral amyloid disease.…”

A single nucleotide polymorphism in the MMP-1 promoter is correlated with histological differentiation of gastric cancer

“…The poor prognosis depends on the degree of stomach wall invasion and on metastatic spread to regional lymph nodes. Degradation of extracellular matrix (ECM) and basement membrane barriers by MMPs plays an important role in tumor invasion and metastasis (Forget et al 1999;Kohn and Liotta 1995;Liotta et al 1991). A prognostic value of MMPs expression in tumor tissue has been reported (McDonnel and Matrisian 1991).…”

A single nucleotide polymorphism in the MMP-9 promoter affects tumor progression and invasive phenotype of gastric cancer

“…Poor prognosis reflects the invasive and metastatic capabilities of cancer cells. Degradation of the extracellular matrix (ECM) and basement membrane barriers by matrix metalloproteinases (MMPs) plays an important role in tumor invasion and metastasis (Forget et al 1999;Kohn and Liotta 1995;Liotta et al 1991). MMP-9 (92-kDa gelatinase, type IV collagenase) is a member of the family of MMP genes, which encode zinc-dependent enzymes that break down ECM through the degradation of type IV collagen (Nagase and Woessner 1999), and promote tumor cell invasion.…”