SummaryThe mechanism of bowel obstruction in colorectal cancer is likely to involve interactions between tumour cells, host fibroblasts and the extracellular matrix. The role of fibroblast-mediated matrix reorganisation in malignant structures of the large bowel was examined in an in vitro collagen matrix model in which tumour cells and fibroblasts were cultured under serum-free conditions. Colon cancer cells secreted a factor(s) which enhanced the ability of colon fibroblasts to contrast a collagen matrix without an associated mitogenic response by the fibroblasts. Within uncontracted collagen gels marked elongation of fibroblast cell processes was observed in the presence of the tumour-derived factor(s). We propose that matrix reorganisation by host fibroblasts in the wall of the human colon is responsible, at least in part, for malignant large bowel obstruction.Current views indicate that the presence of bowel obstruction adversely influences long-term survival from colorectal cancer and the detrimental effect on prognosis does not appear to be simply a function of more advanced tumour stage (Phillips et al., 1985;Chapuis et al., 1985;Fielding et al., 1986). One possibility is that malignant large bowel obstruction is related to tumour fibrosis since the latter has also been associated with a worse prognosis in rectal cancer (Jass et al., 1986). Although the mechanism of the fibrotic response observed in colorectal cancer remains unclear it is likely to involve not only deposition of new matrix, but also re-organisation of existing stroma.The extracellular matrix is composed largely of collagen, and cell-collagen binding is thought to be mediated by glycoprotein attachment molecules and proteoglycans (Yamada et al., 1985). Human colon carcinomas in organ culture have been found to synthesise proteoglycans and their production in the neoplastic colon appears to be localised to the stromal cell compartment rather than the epithelial compartment lozzo & Wight, 1982). This raises the possibility that colon cancer cells influence binding between host fibroblasts and the surrounding collagen matrix.A characteristic of fibroblasts is their ability to bind strongly to collagen and induce collapse of collagen matrices in vitro. This process is known as collagen lattice contraction, and has been considered analogous to wound contraction in vivo (Bell et al., 1979;Steinberg et al., 1980). Previous work undertaken in our laboratory has shown that human colon cancer cells from established cell lines do not cause significant collagen lattice contraction in vitro in contrast to normal human colon fibroblasts (Agrez, 1989a Fibroblast-mediated contraction of collagen discs Preparation of collagen gels Native type collagen was prepared by acetic acid extraction from rat tail tendons according to the method reported by van Bockxmeer and Martin (1982), and protein concentration estimated (Bio-RAD protein microassay, Bio-RAD Laboratories, CA, USA), according to a modification of the Lowry method (Lowry, et al., 1951). Collagen...