title: Redundancy of autocrine loops in human rhabdomyosarcoma cells: induction of differentiation by suramin.
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.
authors.affiliation: Istituto di Cancerologia, Università di Bologna, Italy.
authors.forename: C
authors.initials: C
authors.lastname: De Giovanni
authors.forename: C
authors.initials: C
authors.lastname: Melani
authors.forename: P
authors.initials: P
authors.lastname: Nanni
authors.forename: L
authors.initials: L
authors.lastname: Landuzzi
authors.forename: G
authors.initials: G
authors.lastname: Nicoletti
authors.forename: F
authors.initials: F
authors.lastname: Frabetti
authors.forename: C
authors.initials: C
authors.lastname: Griffoni
authors.forename: M P
authors.initials: MP
authors.lastname: Colombo
authors.forename: P L
authors.initials: PL
authors.lastname: Lollini
mesh_terms: D001483:Base Sequence; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division; D006801:Humans; D008969:Molecular Sequence Data; D012208:Rhabdomyosarcoma / Q000473:pathology*; D013498:Suramin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D013498:Suramin