Mechanism of action of the migration stimulating factor produced by fetal and cancer patient fibroblasts: Effect on hyaluronic acid synthesis |
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Authors: | S L Schor A M Schor A M Grey J Chen G Rushton M E Grant I Ellis |
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Institution: | (1) Department of Cell and Structural Biology, University of Manchester, M13 9PL Manchester;(2) Department of Biochemistry and Molecular Biology, University of Manchester, M13 9PL Manchester;(3) CRC Department of Medical Oncology, Christie Hospital, Wilmslow Road, M20 9BX Manchester |
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Abstract: | Summary We have previously demonstrated that confluent fetal fibroblasts migrate into three-dimensional collagen gels to a significantly
greater extent than their normal adult counterparts. Recent studies have revealed that this behavioral difference results
from the secretion by fetal fibroblasts of a soluble migration-stimulating factor (MSF) which acts on these cells in an autocrine
fashion. Adult fibroblasts do not produce MSF but remain responsive to it. Skin fibroblasts from cancer patients resemble
fetal fibroblasts (rather than normal adult cells) with respect to their migratory behavior on collagen gels and continued
production of MSF. This communication is concerned with elucidating the biochemical basis of MSF activity. Data are presented
indicating that a) hyaluronic acid is required for the elevated migratory activity displayed by confluent fetal and breast
cancer patient skin fibroblast; b) adult fibroblasts exhibit a bell-shaped dose-response to MSF, with maximal stimulation
of migration observed at a concentration of 10 ng/ml; c) the migratory activity of adult fibroblasts pre-incubated with MSF
remains high in the absence of additional factor: and d) MSF affects both the quantity and size class distribution of hyaluronic
acid synthesized by adult fibroblasts. We have previously speculated that the persistent fetal-like fibroblasts of breast
cancer patients play a direct role in disease pathogenesis by perturbing normal epithelial-mesenchymal interactions. The observations
reported here suggest that MSF-induced alterations in hyaluronic acid synthesis may contribute to the molecular basis of such
perturbations.
This work was funded by grants from the Cancer Research Campaign (CRC) and Medical Research Council (MRC), London, England. |
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Keywords: | fibroblasts hyaluronic acid cell migration breast cancer fetal development migration stimulating factor |
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