Redundancy of autocrine loops in human osteosarcoma cells

Stefania Benini, Nicola Baldini, Maria Cristina Manara, Tokuhiro Chano, Massimo Serra, Simona Rizzi, Pier Luigi Lollini, Piero Picci, Katia Scotlandi

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)581-588
Number of pages8
JournalInternational Journal of Cancer
Volume80
Issue number4
DOIs
Publication statusPublished - Feb 4 1999

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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