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Systemic IGF‐I administration stimulates the in vivo growth of early, but not advanced, renal cell carcinoma
Author(s) -
Rosendahl Ann H.,
Holly Jeff M.P.,
Celander Mona,
Forsberg Göran
Publication year - 2008
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.23642
Subject(s) - renal cell carcinoma , growth factor , neovascularization , tumor progression , in vivo , medicine , systemic administration , insulin like growth factor , endocrinology , cell growth , cancer research , cancer , insulin like growth factor 2 , carcinoma , angiogenesis , biology , receptor , genetics , microbiology and biotechnology
Insulin‐like growth factor I (IGF‐I) is a potent mitogen and antiapoptotic factor. Although elevated serum IGF‐I levels have been associated with increased cancer risk, it is not yet clear whether IGF‐I sensitivity is sustained throughout tumor progression. To evaluate the biological effects of IGF‐I during renal cell carcinoma (RCC) establishment and progression, we administered recombinant human IGF‐I to severe combined immuno‐deficient mice bearing early or more established Caki‐2 human RCC tumors. IGF‐I significantly enhanced the tumor growth 2.4‐fold when administered early after tumor inoculation. This IGF‐I‐induced growth was accompanied with enhanced tumor cell proliferation, tumor vascularization, as well as increased intratumoral insulin‐like growth factor binding protein 3 (IGFBP‐3) and pSmad2 levels. In contrast, IGF‐I administrated to more established RCC tumors showed no effect on tumor growth, with subsequently much lower Ki‐67, IGFBP‐3 and pSmad2 levels. Taken together, these data suggest that systemic IGF‐I has potent actions during early RCC tumor development with a sustained long‐term effect on proliferation and neovascularization although with progression, later tumors appear to become desensitized to systemic IGF‐I effects. © 2008 Wiley‐Liss, Inc.