Murine osteosarcoma primary tumour growth and metastatic progression is maintained after marked suppression of serum insulin-like growth factor I

Sung Hyeok Hong, Joseph Briggs, Rachel Newman, Karen Hoffman, Arnulfo Mendoza, Derek LeRoith, Lee Helman, Shoshana Yakar, Chand Khanna

Research output: Contribution to journalArticle

Abstract

The insulin-like growth factor I (IGF-I) signaling pathway has been shown to play an important role in several aspects of cancer biology, including metastasis. The aim of this study was to define the contribution of serum (endocrine) and local (tumour microenvironment) IGF-I on osteosarcoma tumour growth and metastasis, a cancer that is known to be dependent on the IGF-I axis. To test this hypothesis, we evaluated the primary tumour growth and metastatic progression of K7M2 murine osteosarcoma cells injected to a genetically engineered mouse [liver-specific IGF-I de-ficient (LID)] in which serum IGF-I levels are reduced by 75%, while maintaining expression of IGF-I in normal tissues. We first demonstrated that IGF-I in the tumour and the tumour-microenvironment were maintained in the LID mice. Within this designed model, there was no difference in primary tumour growth or in pulmonary metastasis in LID mice compared to control mice. Furthermore, there was no difference in the number or localization of single metastatic cells immediately after their arrival in the lungs of LID mice and control mice, as analysed by single cell video microscopy. Collectively, these data suggest that marked reduction in serum IGF-I is not sufficient to slow the progression of either primary or metastatic models of osteosarcoma.

Original languageEnglish (US)
Pages (from-to)2042-2049
Number of pages8
JournalInternational Journal of Cancer
Volume124
Issue number9
DOIs
StatePublished - May 1 2009

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Keywords

  • Insulin-like growth factor I
  • Murine
  • Osteosarcoma
  • Pulmonary metastasis
  • Tumour microenvironment

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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