Analysis of growth factor-dependent signalling in human epithelioid sarcoma cell lines: clues to the role of autocrine, juxtacrine and paracrine interactions in epithelioid sarcoma

Human epithelioid sarcoma (ES) is an extremely aggressive soft tissue tumou r of unknown histogenesis. Although growth factor-dependent signalling casc ades significantly affect the biological behaviour of malignant tumours, li ttle is known so far about their role in human ES. The present investigatio n, therefore, analyses the coexpression and function of different growth fa ctors and their receptors in the human ES cell line GRU-1 and its clonal su bpopulalions (GRU-1A, GRU-1B and GRU-1C). As shown by Northern blot, flow c ytometry, immunocytochemistry and MTT assay, all ES cell lines expressed tr ansforming growth factor (TGF)-alpha and the epidermal growth factor recept or. (EGF-R). Although no response to exogenous TGF-alpha was observed, anta gonistic anti-EGF-R antibodies (at 20 mu g/ml) induced significant (P < 0.0 5) growth inhibition in all cell lines. All cell lines showed coexpression of platelet-derived growth factor (PDGF)-A and the corresponding receptors. Neutralisation of ES-derived PDGF by anti-hPDGF antibodies resulted in sig nificant (P<0.05) growth inhibition of all clonal subpopulations. Although all cell lines expressed TGF-beta(1) as well as TGF-beta type I and type II receptors (TGF-BI-R and TGF-BII-R), growth inhibition (P < 0.05) by exogen ous TGF-beta(1) was achieved in the clonal subpopulations only and not in t he parental cell line. No ES cell line expressed acidic fibroblast growth f actor (FGF) but stimulation of FGF type 3 and type 4 receptors (FGF-3R and FGF-4R) by exogenous acidic FGF (aFGF) resulted in a marked (P < 0.05) acce leration of proliferation in all cell lines. In conclusion, our investigati on suggests an intricate network of autocrine, juxtacrine and paracrine sig nalling between ES tumour cells and adjacent non-neoplastic stromal cells. (C) 2000 Elsevier Science Ltd. All rights reserved.