Abstract

Three human rhabdomyosarcoma cell lines were used to investigate the presence of autocrine loops based on the production of insulin-like growth factor (IGF)-II, basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF)/transforming growth factor (TGF)-alpha and of their corresponding receptors, and whether these loops affect cell proliferation and myogenic differentiation. Two cell lines, RD/18 and CCA, deriving from tumours of the embryonal histotype, showed the presence of both growth factors and receptors which make possible three different autocrine loops, while the alveolar RMZ-RC2 cell line lacked that based on the EGF receptor. Culture of rhabdomyosarcoma cells in the presence of specific blocking antibodies, directed to a component of single autocrine loops, inhibited cell proliferation (up to 50%), without inducing myogenic differentiation. Suramin, a drug which non-selectively interferes with the binding of growth factors to their cellular receptors, was used to block all the autocrine loops simultaneously. In CCA and RMZ-RC2 cells suramin was able to induce a significant increase (up to 3-fold) in the proportion of myosin-positive cells over control cultures. Therefore rhabdomyosarcoma cells of embryonal and alveolar histotype can show a redundancy of growth-sustaining autocrine loops. Suramin could interfere with them by acting on both growth inhibition and induction of myogenic differentiation.

Highlights

  • Summary Three human rhabdomyosarcoma cell lines were used to investigate the presence of autocrine loops based on the production of insulin-like growth factor (IGF}-11, basic fibroblast growth factor and epidermal growth factor (EGF)/transforming growth factor

  • RD 18 and CCA, deriving from tumours of the embryonal histotype, showed the presence of both growth factors and receptors which make possible three different autocrine loops. while the alveolar RMZ-RC2 cell line lacked that based on the EGF receptor

  • A drug which non-selectively interferes with the binding of growth factors to their cellular receptors, was used to block all the autocrine loops simultaneously

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Summary

Cells and culture conditions

Human rhabdomyosarcoma cell lines used were RD; 18 and CCA, derived from tumours of the embryonal histotype (De Giovanni et a/., 1989, 1993), and RMZ-RC2, derived from an alveolar rhabdomyosarcoma (Nanni et a/., 1986). 7% carbon dioxide atmosphere in 25 cm flasks (NUNC, Denmark)

Growth factor and receptors
EGF b
Proliferation and differentiation experiments
Autocrine growth factor production
Antibody specificity
Days a
Differentiation therapy of rlwbdomyosarcoma
Cell line
ARNOLD HH

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