Systemic effects of insulin-like growth factor-II produced and released from Wilms tumour tissue
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The concentration of mRNA of insulin-like growth factor-II is (IGF-II) much elevated in some embryonic tumours such as Wilms tumour (nephroblastoma). In order to prove whether or not IGF-II is produced by the tumour tisue, IGF-II was extracted from freshly frozen tissue of Wilms tumour and hepatoblastoma. Normal adjacent tissue of kidney and liver was used as a control. The total IGF-II in Wilms tumour was 548.4±77.4 ng/g (n=7) compared to 112.8±38.2 ng/g (n=5) in kidney. In two hepatoblastomas, it was 96.1±22.8 ng/g compared to 30.1±14,2ng/g in normal liver. Small pieces of fresh primary tissue of several Wilms tumours were successfully transplanted into immunodeficient nude mice. In serum of tumour-bearing mice IGF-II was elevated compared to normal mice. Liver weight of tumour bearing mice was higher than that of control mice (2.29±0.4g and 2.02±0.06 g;P<0.005). This was also found for kidney weight (0.58±0.01 g vs. 0.51±0.01 g in controls,P<0.001). In contrast, serum glucose (9.73±0.29 mmol/l compared to 11.80±0.42 mmol/l in controls,P<0.0005) was decreased. However, there was no significant difference in nose-tail length of tumour-bearing compared to control mice. These results demonstrate that besides the highly increased IGF-II-mRNA, the synthesis of the peptide IGF-II and its release into circulation are also elevated in Wilms tumour transplanted into nude mice. Elevated circulating IGF-II is likely to stimulate growth of some inner organs and has a glucose lowering effect but does no stimulate skeletal growth. This is further evidence for the importance of IGF-II as a growth factor.
Key wordsIGF-II Hepatoblastoma Nephroblastoma Tumour hypoglycaemia
insulin-like growth factor II
insulin-like growth factor I
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