TY - JOUR
T1 - Redundancy of autocrine loops in human osteosarcoma cells
AU - Benini, Stefania
AU - Baldini, Nicola
AU - Manara, Maria Cristina
AU - Chano, Tokuhiro
AU - Serra, Massimo
AU - Rizzi, Simona
AU - Lollini, Pier Luigi
AU - Picci, Piero
AU - Scotlandi, Katia
PY - 1999/2/4
Y1 - 1999/2/4
N2 - With the aim of identifying innovative therapeutic strategies for osteosarcoma patients who are refractory to conventional chemotherapy, we analyzed the in vitro effects of the blockage of autocrine circuits. Since the insulin-like growth factor-I receptor (IGF-IR)-mediated loop is relevant to the growth of osteosarcoma, we analyzed the activity of the IGF-IR- blocking antibody αIR3 in both sensitive and multidrug-resistant osteosarcoma cell lines. Only limited effects, however, were observed, suggesting the simultaneous existence of other autocrine circuits. Indeed, in a representative panel of 12 human osteosarcoma cell lines, in addition to the IGF-IR-mediated circuit, we demonstrated also a loop mediated by epidermal growth factor receptor as well as the presence of nerve growth factor, low-affinity nerve growth factor receptor as well as tyrosine receptor kinase A in the great majority of osteosarcomas. Therapies based on the inhibition of single circuits may have only limited effects in osteosarcoma, whereas the use of suramin, a drug which, besides other activities, non-selectively interferes with the binding of growth factors to their receptors, appears as a promising alternative, in both sensitive and drug-resistant osteosarcoma cells.
AB - With the aim of identifying innovative therapeutic strategies for osteosarcoma patients who are refractory to conventional chemotherapy, we analyzed the in vitro effects of the blockage of autocrine circuits. Since the insulin-like growth factor-I receptor (IGF-IR)-mediated loop is relevant to the growth of osteosarcoma, we analyzed the activity of the IGF-IR- blocking antibody αIR3 in both sensitive and multidrug-resistant osteosarcoma cell lines. Only limited effects, however, were observed, suggesting the simultaneous existence of other autocrine circuits. Indeed, in a representative panel of 12 human osteosarcoma cell lines, in addition to the IGF-IR-mediated circuit, we demonstrated also a loop mediated by epidermal growth factor receptor as well as the presence of nerve growth factor, low-affinity nerve growth factor receptor as well as tyrosine receptor kinase A in the great majority of osteosarcomas. Therapies based on the inhibition of single circuits may have only limited effects in osteosarcoma, whereas the use of suramin, a drug which, besides other activities, non-selectively interferes with the binding of growth factors to their receptors, appears as a promising alternative, in both sensitive and drug-resistant osteosarcoma cells.
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U2 - 10.1002/(SICI)1097-0215(19990209)80:4<581::AID-IJC16>3.0.CO;2-O
DO - 10.1002/(SICI)1097-0215(19990209)80:4<581::AID-IJC16>3.0.CO;2-O
M3 - Article
C2 - 9935160
AN - SCOPUS:0033521852
VL - 80
SP - 581
EP - 588
JO - International Journal of Cancer
JF - International Journal of Cancer
SN - 0020-7136
IS - 4
ER -