Murine osteosarcoma primary tumour growth and metastatic progression is maintained after marked suppression of serum insulin-like growth factor I.
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 deficient (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.
Hong
Sung-Hyeok
SH
Pediatric Oncology Branch, Centre for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Briggs
Joseph
J
Newman
Rachel
R
Hoffman
Karen
K
Mendoza
Arnulfo
A
LeRoith
Derek
D
Helman
Lee
L
Yakar
Shoshana
S
Khanna
Chand
C
D000818:Animals; D001859:Bone Neoplasms / Q000097:blood / Q000235:genetics / Q000473:pathology*; D049109:Cell Proliferation; D018450:Disease Progression; D005260:Female; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000502:physiology*; D019426:Integrases / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms / Q000097:blood / Q000378:metabolism / Q000556:secondary*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D012516:Osteosarcoma / Q000097:blood / Q000235:genetics / Q000556:secondary*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D047368:Tumor Burden; D014407:Tumor Cells, Cultured
C519530:insulin-like growth factor-1, mouse; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1; D051057:Proto-Oncogene Proteins c-akt; C045073:Cre recombinase; D019426:Integrases