Stimulation of tumor growth by recombinant human insulin-like growth factor-I (IGF-I) is dependent on the dose and the level of IGF-I receptor expression

Andrew A. Butler, Vicky A. Blakesley, Maria Tsokos, Vasiliki Pouliki, Teresa L. Wood, Derek LeRoith

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66 Scopus citations

Abstract

The insulin-like growth factors (IGF) I and II regulate metabolism, mitogenesis, differentiation, and apoptosis. The therapeutic uses of IGF-I have been discussed extensively; however, excessive activity of the IGF ligands and IGF-I receptor has been suggested as a factor in tumorigenesis. The inhibition of apoptosis by IGF-I is believed to be particularly important for the stimulation of tumor growth. This study examined whether systemic recombinant human IGF-I (rhIGF-I) therapy affects the growth of fibrosarcomas derived from fibroblasts expressing the IGF-I receptor at high or naturally occurring densities (1.9 x 105 compared with 1.6 x 104 IGF-I receptors/cell) in athymic nude mice. Treatment with 4 or 10 mg/kg rhIGF-I resulted in a marked reduction in the tumor latency and stimulated the growth of fibrosarcomas that overexpressed the IGF-I receptor. The latency and growth of fibrosarcomas expressing parental levels of the IGF-I receptor were not affected by rhIGF-I therapy. Analysis of mitosis by histone H3 mRNA in situ hybridization and of apoptosis by terminal deoxynucleotidyl transferase- mediated nick end labeling assay indicated that rhIGF-I-stimulated tumor growth was associated with a marked increase in mitogenesis; however, there was no evidence for any significant effect on apoptosis. These data imply that: (a) systemic rhIGF-I can stimulate the growth of tumors directly by stimulating mitosis; and (b) a reasonable level of IGF-I receptor expression is required for stimulation of tumor growth by systemic rhIGF-I.

Original languageEnglish (US)
Pages (from-to)3021-3027
Number of pages7
JournalCancer Research
Volume58
Issue number14
StatePublished - Jul 15 1998
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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