Collagenase immunolocalization studies of cutaneous secondary melanomas

Abstract

Summary.-Immunoreactive collagenase has been demonstrated in 5/14 specimens of cutaneous secondary melanomas. In contrast, very little enzyme was seen in 10 specimens of normal human skin. All specimens were fixed within minutes of excision. These findings support the hypothesis that collagenase facilitates connective-tissue breakdown which is associated with tumour invasiveness and metastatic spread.

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

“…Control assays included: (1) buffer alone which routinely released no more than 3% solubilisation of total counts available, (2) mast cell products at the test dilution which released approximately 6% of total counts, and (3) trypsin (5 jg ml-1) which released no more than 8% of total counts thereby confirming the native integrity of the collagen substrate. The enzyme activity released by both fibroblast and tumour cell cultures was inhibited by the metal chelator ethylene diamine tetra-acetic acid, and at 25°C produced the typical 3:4 cleavage product of type I collagen monomers as described previously (Dabbous et al, 1977;Woolley et al, 1984).…”

“…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. Previous immunolocalisation studies have demonstrated that collagenase production at the tumour edge is often microenvironmental in nature, but the cellular origin of the enzyme may depend to some extent on the type or tissue location of the invasive tumour (Woolley, 1982;Woolley & Grafton, 1980;Barsky et al, 1983). Further enzyme localisation studies in conjunction with the identification of specific host cells should help to elucidate which cellular interactions are involved in generating local collagenolysis in vivo.…”

“…We report here our finding of numerous mast cells at the tumour periphery, an observation frequently associated with disruption or lysis of the local collagenous matrix. Mast cells have been shown to contain soluble products which stimulate fibroblasts to produce increased amounts of collagenase Pilarisetti et al, 1983;Atkins et al, 1985), and mast cell products also have the ability to stimulate monocyte-macrophages to produce interleukin-1 (Yoffe et al, 1985), a factor known to stimulate collagenase production by various mesenchymal cells (see Woolley et al, 1984). Since mast cells apparently have the potential to modulate collagenolysis we have also examined and report here the in vitro effects of soluble mast cell products on the collagenolytic behaviour of rat stromal fibroblasts and tumour cells.…”

Collagen production by macrophages in tumour encapsulation and dormancy

“…Tumour factors such as phenotypic diversity (Weinhold et al, 1979), tumour invasive factors (e.g. collagenase) (Woolley, 1982;Pauli et al, 1983), antigen shedding (Davey et al, 1976), and immunosuppressive factors (Eccles & Alexander, 1975), may be involved when growth resumes.…”

Correlation of collagenase secretion with metastatic-colonization potential in naturally occurring murine mammary tumours

“…They also indicate a plausible mechanism for the morphological observation of removal of intercellular materials in primary and secondary tumour infiltration and expansion (Tarin, 1972(Tarin, , 1976 and this interpretation is supported by the immunocytochemical localization of the enzyme at the tumour-stromal interface (Woolley & Grafton, 1980).…”