Redundancy of autocrine loops in human rhabdomyosarcoma cells: induction of differentiation by suramin.
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.
De Giovanni
C
C
Istituto di Cancerologia, Università di Bologna, Italy.
Melani
C
C
Nanni
P
P
Landuzzi
L
L
Nicoletti
G
G
Frabetti
F
F
Griffoni
C
C
Colombo
M P
MP
Lollini
P L
PL
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
D013498:Suramin