Fetal and cancer patient fibroblasts secrete a soluble migration stimulating factor not produced by normal adult cells

1987 ◽  
Vol 11 (3) ◽  
pp. 231
Author(s):  
S SCHOR ◽  
A SCHOR ◽  
G RUSHTON ◽  
L MCCORMICK
1988 ◽  
Vol 90 (3) ◽  
pp. 391-399 ◽  
Author(s):  
S.L. Schor ◽  
A.M. Schor ◽  
A.M. Grey ◽  
G. Rushton

We have previously reported that (1) the migration of foetal and adult fibroblasts into three-dimensional collagen matrices is differentially affected by cell density, and (2) skin fibroblasts from cancer patients commonly display a foetal-like mode of migratory behaviour. Data presented here indicate that differences in the migration of these cell types are particularly apparent in cultures plated at high density (i.e. at cell confluence); under these conditions, foetal fibroblasts and the foetal-like fibroblasts of cancer patients migrate into the three-dimensional collagen matrix to a significantly greater extent than do normal adult cells. In this initial study concerned with the biochemical basis of these observations, we report that medium conditioned by either foetal or cancer patient fibroblasts stimulates the migration of confluent adult cells. This stimulation of migration is specific to confluent cells, as the migration of subconfluent adult fibroblasts is unaffected by these conditioned media. Gel filtration chromatography of foetal fibroblast-conditioned medium indicates that migration-stimulating activity is recovered in a single peak with an apparent molecular mass in the range of 50–60 (X 10(3]. The active migration stimulating factor (MSF) in both foetal and cancer patient fibroblast-conditioned media appears to be a protein stable at acid pH, but inactivated by heat, alkaline pH and reductive alkylation. MSF produced by foetal and cancer patient fibroblasts is presumably responsible for the characteristically elevated levels of migration displayed by these cells in confluent culture, thereby suggesting an autocrine mode of action for this factor.(ABSTRACT TRUNCATED AT 250 WORDS)


1988 ◽  
Vol 90 (3) ◽  
pp. 401-407 ◽  
Author(s):  
S.L. Schor ◽  
A.M. Schor ◽  
G. Rushton

We have previously reported that foetal and adult fibroblasts display distinctive migratory phenotypes when cultured on three-dimensional collagen gels. Both skin and tumour-derived fibroblasts from a significant proportion of patients with breast cancer were subsequently observed to display foetal-like migratory behaviour. In the accompanying paper concerned with the biochemical basis of these observations, we presented evidence that foetal fibroblasts and the foetal-like fibroblasts of cancer patients produce a soluble migration-stimulating factor (MSF) not made by normal adult cells. Data are presented here indicating that: (1) the spontaneous foetal-to-adult transition in migratory phenotype that foetal fibroblasts undergo after approximately 50–55 population doublings in vitro is correlated with a cessation of MSF production; (2) breast cancer patient fibroblasts do not undergo such a phenotypic transition and continue to produce MSF for their entire in vitro lifespan. These foetal-like cancer patient fibroblasts do, however, resemble normal adult cells by a number of other criteria, including population doubling potential, enhanced migration in the presence of serum compared to platelet-poor plasma, saturation cell density and morphology in confluent culture. These data indicate that the fibroblasts of breast cancer patients express a mixture of both foetal and adult phenotypic characteristics. Such a finding is consistent with published information indicating that foetal-to-adult transitions in various fibroblast phenotypic characteristics occur in a temporally disparate fashion during normal development, and further imply that cancer patient fibroblasts have undergone only certain of these transitions.


1977 ◽  
Vol 63 (4) ◽  
pp. 359-365
Author(s):  
Sylvie Ménard ◽  
Maria I. Colnaghi ◽  
Giuseppe Della Porta

Normal adult C57BL/6J fibroblasts, cultured to saturation density and therefore in resting phase, were harvested by EDTA, treated with trypsin at various concentrations for different lengths of time and then tested for absorbing capacity of a C57BL/He anti-embryo serum, the residual cytotoxic activity being measured by a 51Cr release assay on a C57BL/He lymphosarcoma known to carry embryonic antigens. A weak proteolytic treatment (0.05 – 0.25 % trypsin for 5–10 min) uncovered structures which absorbed over 40 % activity of the anti-embryo serum. The treated fibroblasts partially retained the absorbing capacity for an antihistocompatibility serum. Higher doses or longer exposure to trypsin progressively inactivated the absorbing capacity of fibroblasts for both antisera. Trypsin treatment of fibrosarcoma cells, which when untreated completely absorbed the anti-embryo serum, decreased their absorbing capacity. Additionally, normal untreated fibroblasts in growing phase were found to absorb the anti-embryo serum.


2007 ◽  
Vol 282 (49) ◽  
pp. 35530-35535 ◽  
Author(s):  
Christopher J. Millard ◽  
Ian R. Ellis ◽  
Andrew R. Pickford ◽  
Ana M. Schor ◽  
Seth L. Schor ◽  
...  

The motogenic activity of migration-stimulating factor, a truncated isoform of fibronectin (FN), has been attributed to the IGD motifs present in its FN type 1 modules. The structure-function relationship of various recombinant IGD-containing FN fragments is now investigated. Their structure is assessed by solution state NMR and their motogenic ability tested on fibroblasts. Even conservative mutations in the IGD motif are inactive or have severely reduced potency, while the structure remains essentially the same. A fragment with two IGD motifs is 100 times more active than a fragment with one and up to 106 times more than synthetic tetrapeptides. The wide range of potency in different contexts is discussed in terms of cryptic FN sites and cooperativity. These results give new insight into the stimulation of fibroblast migration by IGD motifs in FN.


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