Role of collagenases in tumor cell invasion

Abstract

Collagenases are a family of metalloproteinases which may play a role in facilitating tumor cell invasion of the extracellular matrix. Tumor cells traverse two types of extracellular matrix: basement membranes and interstitial stroma, at multiple stages of the metastatic process. The matrix is a dense meshwork of collagen, proteoglycans, elastin and glycoproteins. Normally the matrix does not contain open spaces large enough for cell movement. Therefore numerous investigators have postulated that collagenolytic proteases, secreted by tumor cells or associated host cells, breakdown the extracellular matrix during tumor cell invasion. A large number of animal and human tumors have been shown to contain collagenase at a higher level than corresponding benign tissues. Separate collagenolytic metalloproteinases have been identified which degrade specific types of collagen. A basement membrane collagenolytic protease was shown to be elevated in a series of metastatic murine tumor cells. Immunologic studies using antibodies specific for collagenase have demonstrated that in vivo, tumor cells can produce collagenase. Therefore identification of collagenase in cultured lines of tumor cells is not an artifact of in vitro cultivation. In some cases, tumor cells may induce host cells to produce collagenase. The best evidence to date that collagenases actually play a role in invasion is derived from experiments in which natural collagenase inhibitors block tumor cell invasion of extracellular matrix in vitro.

Diosgenin inhibits osteoclastogenesis, invasion, and proliferation through the downregulation of Akt, IκB kinase activation and NF-κB-regulated gene expression

“…Tumor metastasis depends on the activity of MMPs, COX-2, and adhesion molecules (Liotta et al, 1982). Thus, we investigated whether diosgenin can modulate the tumor cell invasion activity induced by TNF in vitro.…”

Mast cells and matrix degradation at sites of tumour invasion in rat mammary adenocarcinoma

“…Many studies have examined the role of collagenolytic enzymes in tumour invasion and metastatic spread (for reviews see Woolley et al, 1980;Liotta et al, 1982; and recently several investigations have emphasised the importance of tumour:host cell interactions in connective tissue degradation (Tarin, 1976;Dabbous et al, 1977Dabbous et al, ,1983aBiswas, 1982;Henry et al, 1983). The tumour: host interface or 'invasion zone' (Strauli, 1980) of many invasive tumours is variable with regard to the type and relative numbers of host cells.…”

Prognostic impact of urokinase-type plasminogen activator receptor (uPAR) in cytosols and pellet extracts derived from primary breast tumours

“…Proteolytic enzymes of the plasminogen activation system released by the neoplastic cells and/or the surrounding tumour stroma accomplish invasion into the surrounding normal tissue by degradation of basement membranes and extracellular matrix proteins (Liotta et al, 1982;Danø et al, 1985;Mignatti and Rifkin, 1993). Central to this system is the conversion of the abundant zymogen plasminogen into active plasmin, which is able to degrade several extracellular proteins and to activate latent prometalloproteases (Duffy, 1992;Mignatti and Rifkin, 1993;Andreasen et al, 1997).…”