The extracellular matrix of hybrids between melanoma cells and normal fibroblasts.
It has been shown that when malignant tumour cells are fused with normal fibroblasts the suppression of malignancy in the hybrids is linked to their ability to produce a collagenous extracellular matrix in vivo. When, as a consequence of chromosome loss, segregants arise that reacquire malignancy, these do not produce any detectable matrix. In this paper we examine the main components of the extracellular matrix produced in vitro by hybrids between malignant mouse melanoma cells and normal mouse fibroblasts. Hybrids in which malignancy is suppressed synthesize about ten times as much type 1 procollagen as the malignant segregants derived from them; they also retain more fibronectin in the cell layer and release less protease activity into the medium. Malignant segregants more closely resemble the parental melanoma cells in producing fibronectin and mainly types IV and V procollagen. When hybrid cells in which malignancy is initially suppressed are grown continuously in vitro, the production of type I procollagen declines, and the production of type V procollagen and the release of protease activity into the medium increase. These changes, which are associated with the loss from the hybrid cells of both copies of the chromosome 4 derived from the parental fibroblast, predict the reacquisition of malignancy when the cells are inoculated into mice. It is possible that one gene or set of genes located on chromosome 4 determines both the execution of the fibroblast differentiation programme and the suppression of malignancy.
Copeman
M C
MC
Sir William Dunn School of Pathology, University of Oxford, UK.
Harris
H
H
D000818:Animals; D001345:Autoradiography; D002460:Cell Line; D002875:Chromosomes; D005109:Extracellular Matrix / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism; D005353:Fibronectins / Q000096:biosynthesis*; D006822:Hybrid Cells / Q000378:metabolism*; D008545:Melanoma / Q000378:metabolism / Q000473:pathology; D051379:Mice; D010447:Peptide Hydrolases / Q000378:metabolism; D011347:Procollagen / Q000096:biosynthesis*
D005353:Fibronectins; D011347:Procollagen; D010447:Peptide Hydrolases