Advanced

L-iduronate-rich glycosaminoglycans inhibit growth of normal fibroblasts independently of serum or added growth factors

Westergren-Thorsson, G LU ; Persson, S; Isaksson, A LU ; Önnervik, Per-Ola; Malmström, A LU and Fransson, L A LU (1993) In Experimental Cell Research 206(1). p.9-93
Abstract

The effects of various glycosaminoglycans (GAGs) on the growth rate of normal fibroblasts and a fibrosarcoma cell line (HT 1080) were examined. Cells were grown in 96-well microplates in the absence or presence of serum mitogens, epidermal (EGF), platelet-derived (PDGF), acidic fibroblast (aFGF), or basic fibroblast growth factor (bFGF). Cell number was measured by using crystal violet to stain cell nuclei (Westergren-Thorsson, G., Onnervik, P.-O., Fransson, L.-A., and Malmström, A. J. Cell. Phys. 147, 523-530, 1991) and also by using a Coulter counter. In the presence of serum mitogens, L-iduronate (IdoA)-rich GAGs, such as dermatan sulfate, heparin, and highly sulfated heparan sulfate, inhibited proliferation of normal cells (25-35%),... (More)

The effects of various glycosaminoglycans (GAGs) on the growth rate of normal fibroblasts and a fibrosarcoma cell line (HT 1080) were examined. Cells were grown in 96-well microplates in the absence or presence of serum mitogens, epidermal (EGF), platelet-derived (PDGF), acidic fibroblast (aFGF), or basic fibroblast growth factor (bFGF). Cell number was measured by using crystal violet to stain cell nuclei (Westergren-Thorsson, G., Onnervik, P.-O., Fransson, L.-A., and Malmström, A. J. Cell. Phys. 147, 523-530, 1991) and also by using a Coulter counter. In the presence of serum mitogens, L-iduronate (IdoA)-rich GAGs, such as dermatan sulfate, heparin, and highly sulfated heparan sulfate, inhibited proliferation of normal cells (25-35%), whereas HT 1080 cells were unaffected or slightly stimulated. Ham's F-12 supplemented with insulin and transferrin but without growth factors was able to support growth of both cell types. Under these conditions, the IdoA-rich GAGs still suppressed growth of normal cells (40-55%), whereas HT 1080 cells again responded poorly. When growth factors were added proliferation of normal fibroblasts was further stimulated, EGF being the most effective. In the presence of either EGF, PDGF, or bFGF, IdoA-rich GAGs had a sustained inhibitory effect on normal fibroblasts (30-50% at concentrations at or above 10 micrograms/ml). However, in the presence of aFGF, both IdoA-rich and IdoA-poor heparan sulfates enhanced growth (nearly twofold after prolonged exposure) suggesting a stabilization of this growth factor. In general, IdoA-rich GAGs appear to inhibit proliferation of normal cells irrespective of the type of growth factor used. Therefore, GAGs are likely to act directly on cell-derived regulatory components, either before or after internalization. As fibrosarcoma cells were much less sensitive to growth inhibition, they may contain altered receptors for GAGs.

(Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Blood Proteins, Cell Division, Cells, Cultured, Dermatan Sulfate, Epidermal Growth Factor, Fibroblast Growth Factor 1, Fibroblast Growth Factor 2, Fibroblasts, Fibrosarcoma, Glycosaminoglycans, Growth Inhibitors, Growth Substances, Heparitin Sulfate, Humans, Iduronic Acid, Lung, Mitogens, Platelet-Derived Growth Factor, Tumor Cells, Cultured, Journal Article, Research Support, Non-U.S. Gov't
in
Experimental Cell Research
volume
206
issue
1
pages
9 - 93
publisher
Academic Press
external identifiers
  • scopus:0027192138
ISSN
0014-4827
DOI
10.1006/excr.1993.1124
language
English
LU publication?
yes
id
92f56ce4-aacd-473f-93dd-06a521c07d5f
date added to LUP
2017-06-27 14:20:19
date last changed
2017-07-02 05:03:55
@article{92f56ce4-aacd-473f-93dd-06a521c07d5f,
  abstract     = {<p>The effects of various glycosaminoglycans (GAGs) on the growth rate of normal fibroblasts and a fibrosarcoma cell line (HT 1080) were examined. Cells were grown in 96-well microplates in the absence or presence of serum mitogens, epidermal (EGF), platelet-derived (PDGF), acidic fibroblast (aFGF), or basic fibroblast growth factor (bFGF). Cell number was measured by using crystal violet to stain cell nuclei (Westergren-Thorsson, G., Onnervik, P.-O., Fransson, L.-A., and Malmström, A. J. Cell. Phys. 147, 523-530, 1991) and also by using a Coulter counter. In the presence of serum mitogens, L-iduronate (IdoA)-rich GAGs, such as dermatan sulfate, heparin, and highly sulfated heparan sulfate, inhibited proliferation of normal cells (25-35%), whereas HT 1080 cells were unaffected or slightly stimulated. Ham's F-12 supplemented with insulin and transferrin but without growth factors was able to support growth of both cell types. Under these conditions, the IdoA-rich GAGs still suppressed growth of normal cells (40-55%), whereas HT 1080 cells again responded poorly. When growth factors were added proliferation of normal fibroblasts was further stimulated, EGF being the most effective. In the presence of either EGF, PDGF, or bFGF, IdoA-rich GAGs had a sustained inhibitory effect on normal fibroblasts (30-50% at concentrations at or above 10 micrograms/ml). However, in the presence of aFGF, both IdoA-rich and IdoA-poor heparan sulfates enhanced growth (nearly twofold after prolonged exposure) suggesting a stabilization of this growth factor. In general, IdoA-rich GAGs appear to inhibit proliferation of normal cells irrespective of the type of growth factor used. Therefore, GAGs are likely to act directly on cell-derived regulatory components, either before or after internalization. As fibrosarcoma cells were much less sensitive to growth inhibition, they may contain altered receptors for GAGs.</p>},
  author       = {Westergren-Thorsson, G and Persson, S and Isaksson, A and Önnervik, Per-Ola and Malmström, A and Fransson, L A},
  issn         = {0014-4827},
  keyword      = {Blood Proteins,Cell Division,Cells, Cultured,Dermatan Sulfate,Epidermal Growth Factor,Fibroblast Growth Factor 1,Fibroblast Growth Factor 2,Fibroblasts,Fibrosarcoma,Glycosaminoglycans,Growth Inhibitors,Growth Substances,Heparitin Sulfate,Humans,Iduronic Acid,Lung,Mitogens,Platelet-Derived Growth Factor,Tumor Cells, Cultured,Journal Article,Research Support, Non-U.S. Gov't},
  language     = {eng},
  number       = {1},
  pages        = {9--93},
  publisher    = {Academic Press},
  series       = {Experimental Cell Research},
  title        = {L-iduronate-rich glycosaminoglycans inhibit growth of normal fibroblasts independently of serum or added growth factors},
  url          = {http://dx.doi.org/10.1006/excr.1993.1124},
  volume       = {206},
  year         = {1993},
}