Abstract
Wilms tumor is a common embryonic tumor in childhood. Two Wilms tumor-suppressor genes, WT1 and WT2, are located on chromosome 11p, WT2 at 11p15.5 close to the IGF-II gene, which is highly expressed in some Wilms tumors. We established Wilms tumor cell lines to investigate the regulation of tumor cell growth by IGF-II. We demonstrated that Wilms tumor cells produce more IGF-II than normal kidney cells. Both types I and II IGF receptors reside on these cells. In serum-free culture medium, tumor cell growth is reversibly inhibited by suramin via interfering with IGF-II binding. Wilms tumor cell growth is also arrested by IGF binding protein-3, capturing the continuously produced IGF-II, and by αIR-3, a type I IGF receptor-blocking antibody. Thus, we demonstrated the whole loop of elevated synthesis, secretion, receptor binding, and autocrine growth stimulation of IGF-II through type I IGF receptor in Wilms tumor cell cultures. We concluded that IGF-II plays a crucial role in the regulation of growth of this embryonic tumor. Overproduction of IGF-II by the tumor cell is the limiting step for Wilms tumor growth, supporting its important role as an embryonic growth factor.
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Abbreviations
- rhIGF-I and rhIGF-II:
-
recombinant human IGF-I and -II
- IGFBP-3:
-
IGF binding protein-3
- αIR-3:
-
type I IGF receptor antibody
- DMEM:
-
Dulbecco's modified Eagle's medium
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Acknowledgements
The authors are grateful to Dr. T. Torresani and L. Alig-Schuster for their important contributions and technical help to this study.
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Supported by the “Stiftung zur Krebsbekämpfung,” the Roche Research Foundation, the Julius Müller Foundation, the Deutsche Forschungsgemeinschaft (DFG grant Schm 943/1-1), and by the Swiss National Science Foundation (grants 32-29863.90 and 32-39427.93).
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Ren-Qiu, Q., Schmitt, S., Ruelicke, T. et al. Autocrine Regulation of Growth by Insulin-Like Growth Factor (IGF)-II Mediated by Type I IGF-Receptor in Wilms Tumor Cells. Pediatr Res 39, 160–165 (1996). https://doi.org/10.1203/00006450-199601000-00025
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DOI: https://doi.org/10.1203/00006450-199601000-00025
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