EFFECTS ON GLYCOSAMINOGLYCAN SYNTHESIS IN CULTURED HUMAN MESOTHELIOMACELLS OF TRANSFORMING, EPIDERMAL, AND FIBROBLAST GROWTH-FACTORS AND THEIR COMBINATIONS WITH PLATELET-DERIVED GROWTH-FACTOR
Gn. Tzanakakis et al., EFFECTS ON GLYCOSAMINOGLYCAN SYNTHESIS IN CULTURED HUMAN MESOTHELIOMACELLS OF TRANSFORMING, EPIDERMAL, AND FIBROBLAST GROWTH-FACTORS AND THEIR COMBINATIONS WITH PLATELET-DERIVED GROWTH-FACTOR, Experimental cell research, 220(1), 1995, pp. 130-137
Two human mesothelioma cell sublines with fibroblast-like and epitheli
al morphology produce hyaluronan, galactosaminoglycans, and heparan su
lfate in amounts varying with their cell phenotype. The epithelially d
ifferentiated cells synthesize these glycosaminoglycans in 6- to 8-fol
d higher amounts than the fibroblast-like cells, Hyaluronan is mainly
a secretory product (>90%), a considerable proportion of galactosamino
glycans is present in the extracellular medium (>80%), while more of t
he heparan sulfate (50-70%) is cell-associated. In both cell lines the
rates of synthesis of glycosaminoglycans are affected by the addition
of the exogenous growth factors. In fibroblast phenotype cells, TGF-b
eta(2), EGF, and bFGF increase the production of glycosaminoglycans fr
om 1.6- to 2.0-fold, with the exception of HS, which is suppressed by
the addition of bFGF. The combination of these growth factors with Pf)
GF-BB showed that only EGF causes a synergistic action in the synthesi
s of all glycosaminoglycans and that no additive effect is obtained wh
en PDGF-BB is combined with TGF-beta(2) and bFGF. In epithelially diff
erentiated cells, the addition of exogenous TGF-beta(2) and bFGF has n
o significant effect on hyaluronan synthesis, which is increased by EG
F to 45%. The synthesis of galactosaminoglycans is stimulated by EGF a
nd TGF-beta(2) approximately 35%, whereas bFGF has no significant effe
ct. Heparan sulfate production is considerably increased by the additi
on of EGF by 50%, whereas bFGF has no significant effect and TGF-beta(
2) suppresses this synthesis. The combination of the various growth fa
ctors with PDGF-BB showed that only heparan sulfate synthesis is affec
ted. Thus, combining PDGF-BB with TGF-beta(2) and EGF this synthesis i
s increased by 35 and 25%, whereas the combination of bFGF with PDGF-B
B has no further effect. The remarkable differences found between the
two mesothelioma sublines may well be related to the importance of gly
cosaminoglycan-growth factor interactions as a key factor in phenotypi
c cell differentiation. (C) 1995 Academic Press, Inc.