Abstract
Significant numbers of mast cells have been demonstrated histologically around the periphery of the invasive rat mammary adenocarcinoma 13672NF. The number of mast cells at microfoci along the tumour:host tissue junction was significantly greater than that found in normal mammary tissues, and few mast cells were detected within the tumour itself. Mast cell degranulation, often associated with disruption and lysis of the connective tissue matrix, was a common feature in later stages of tumour proliferation. When soluble products derived from purified rat peritoneal mast cells were added to monolayer cultures of rat stromal fibroblasts or tumour cells they stimulated a significant increase in total collagenase production, and the mast cell products were also capable of activating the latent collagenases thus produced. Histological examination indicated that degradation of local collagenous matrix was a common feature of mast cell degranulation, an observation possibly explained by the release of mast cell enzymes and/or the potential of this cell to modulate the expression of collagenolytic activity by surrounding cells. These observations suggest that, at least in some tumours, mast cells contribute to the connective tissue breakdown commonly associated with tumour invasiveness and metastatic spread.
Highlights
Since mast cells apparently have the potential to modulate collagenolysis (Woolley, 1984) we have examined and report here the in vitro effects of soluble mast cell products on the collagenolytic behaviour of rat stromal fibroblasts and tumour cells
Mast cells were found to be randomly dispersed in the connective tissue and between fat deposits of normal rat mammary tissue and most frequently around small blood vessels
Intact mast cells were frequently observed alongside fibroblasts in the connective tissue stroma remote from tumour cells
Summary
Tumour cell lineTumour cell clone, MTLn3, was obtained from the rat 13762NF mammary adenocarcinoma and main-() The Macmillan Press Ltd., 1986 tained in alpha-modified minimum essential medium (AMEM) supplemented with 10% heat inactivated foetal calf serum, HIFCS, (Grand Island Biological Co., Grand Island, NY) as previously described (Neri & Nicolson, 1981; Neri et al, 1982).Fibroblast culturesNormal rat skin fibroblasts (NRS) were established from skin explants of syngeneic newborn rats. MTLn3, was obtained from the rat 13762NF mammary adenocarcinoma and main-. () The Macmillan Press Ltd., 1986 tained in alpha-modified minimum essential medium (AMEM) supplemented with 10% heat inactivated foetal calf serum, HIFCS, (Grand Island Biological Co., Grand Island, NY) as previously described (Neri & Nicolson, 1981; Neri et al, 1982). Normal rat skin fibroblasts (NRS) were established from skin explants of syngeneic newborn rats. The subsequent fibroblast monolayers were grown in AMEM containing 10% HIFCS at 37°C in 5% CO2 and 95% humidified air. Tumour cells (5 x 105) were injected s.c. into the mammary fat pad of pathogenfree, female Fischer 344 rats, anaesthetised with methoxyflurane. At later stages the tumour cell mass varied in size and shape, but often measured more than 2 cm in its greatest dimension
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