Collagenolytic mechanisms in tumor cell invasion

Abstract

Connective tissue stroma and basement membrane structures probably present natural barriers to the migration of tumor cells. It has therefore been proposed that collagenolytic enzymes are required to facilitate the spread and invasion of tumor cells into host tissues. The collagenases and cathepsin B-like enzymes are thought to be involved, but the cellular source of collagenolytic activity at the tumor: host interface or 'invasion zone' remains obscure in most cases. The 'invasion zone' of different tumors is very variable with regard to the type and numbers of host or tumor cells, as well as the type of collagenous matrix, and few generalities can be made. The existence within a tumor of specialised subpopulations of cells which have different metastatic potential has been postulated. As a consequence it seems plausible that the phenotypic expression of highly invasive or metastatic tumor cells should include the potential for generating collagenolytic activity. Immunolocalisation studies have demonstrated the production of type I and type IV collagenases at sites of tumor invasion, but it does not appear to be a continuous process and only a small proportion of tumor and/or host cells elaborate enzyme at any one moment. Collagenase production is invariably microenvironmental in nature and it seems likely that local host:tumor cell interactions are important in modulating collagenolysis. Macrophages and mast cells have been shown to stimulate collagenase expression by tumor and stromal cells in vitro, and it is proposed that these cells may assume a contributory role for the induction of collagenolytic activity in vivo. The collagenolytic mechanisms that operate at micro-foci of host:tumor junctions probably depend upon the type of collagen, the cellular composition and the extracellular ionic conditions of each invasion site. Either tumor or host cells may elaborate enzymes, this being dependent upon the type and/or tissue location of the invasive tumor.

Immunohistochemical expression of SKALP/elafin in squamous cell carcinoma of the oesophagus

“…At present, only limited numbers of patients can be cured by conventional therapy, such as surgical resection, irradiation and chemotherapy, one reason being that oesophageal cancer has an extremely high potential for invasion into the surrounding organs and for metastasis. Several proteases produced by the cancer cell itself have been reported to be associated with cancer invasion and metastasis (Liotta et al, 1980(Liotta et al, , 1986Wooley, 1984;Nakajima et al, 1987;Reich et al, 1988;Basset et al, 1990). Also several kinds of specific inhibitors of such proteases have been shown to inhibit cancer invasion and metastasis (Baker et al, 1990;Cajot et al, 1990;Albini et al, 1991;Declerck et al, 1992;Kennedy, 1994;Kobayashi et al, 1994Kobayashi et al, , 1995.…”

12-O-tetradecanoyl-phorbol-13-acetate induction of the human collagenase gene is mediated by an inducible enhancer element located in the 5'-flanking region.

“…This gene appears to have a role in both physiologic and pathologic inflammatory reactions (40,42,54). Its product, initially designated XHF1 (33), is the major secreted protein of human skin fibroblasts induced in response to TPA, mitomycin C, or UV irradiation (3,23,33).…”

Gem-diamine 1-N-iminosugars as versatile glycomimetics: synthesis, biological activity and therapeutic potential

“…[49][50][51][52][53] Proteolytic enzymes (heparanase and matrix metalloproteinases) secreted by tumor cells are capable of degrading ECM and BM components, and their activities are closely related to the metastasis potential of malignant cells. [54][55][56][57][58][59][60] The inhibitory effects of uronic acid-type gem-diamine 1-N-iminosugars that have inhibitory activities against exo-uronidase, heparanase, sulfotransferase and sialyltransferase were also evaluated on tumor metastasis using the experimental and spontaneous pulmonary metastasis in mice.…”