The tumorIGF-II content was extremely high, messenger RNA (mRNA) for IGF-II showed a 100-fold increase in expression compared with normal human liver tissue.
Control fibroblasts respond to mannose 6-phosphate, IGF I, IGF II and tumor promoting phorbol esters with a rapid redistribution of mannose 6-phosphate/IGF II receptors from internal membranes to the cell surface.
These findings provide a molecular basis for overexpression of IGF-II in Wilms tumors and suggest that WT1 negatively regulates blastemal cell proliferation by limiting the production of a fetal growth factor in the developing vertebrate kidney.
Within the meningiomas, only a small number of cells highly expressed insulin-like growth factor II immunoreactive material, and this could be evidence for a paracrine mechanism in these tumors.
Furthermore, fetal insulin-like growth factor II mRNAs were observed in five tumors and six nontumorous cirrhotic areas not expressing alpha-fetoprotein mRNA.
There is now convincing evidence that some tumors secrete sufficient IGF-II to have systemic endocrine effects as recognized as nonislet cell tumor hypoglycemia.
Sections of normal liver and tumor and non-tumor-bearing liver disease tissue were hybridized in situ with [35S]-labeled insulin-like growth factor II oligonucleotide probe.
An examination of human neuroblastoma tumor tissues for IGF-II gene expression using in situ hybridization histochemistry revealed that IGF-II is expressed by tumor cells in only 5 of 21 neuroblastomas, but is detectable in cells of nonmalignant tissues including adrenal cortical cells, stromal fibroblasts, and eosinophils in all 21 tumors.
Although total serum insulin-like growth factor II (IGF-II) levels in both groups of tumor patients were lower than normal, tumor tissue from hypoglycemic patients contained levels of IGF-II mRNA that were 10-20-fold higher than those present in normal liver.
Because an increased percentage of IGF-II in serum of patients with hypoglycemia who have other tumors is present as partially processed pro-IGF-II ("big" IGF-II), we passed sera of patients with hypoglycemia and patients with euglycemia with hepatomas through acidic Bio-Gel P-60 columns.
The fetal expression patterns of the N-myc and IGF-II mRNAs are reflected by the types of tumors known to express the corresponding genes during postnatal life such as Wilms' tumor.
We suggest that the primary event in tumor-induced hypoglycemia is overproduction of IGF-II by the tumor, which gives rise to hypoglycemia by a dual mechanism: increased glucose utilization mediated by the insulin-like actions of IGF-II and inhibition of GH secretion.