INCREASED INSULIN-LIKE GROWTH-FACTOR BINDING PROTEIN-2 (IGFBP-2) GENE-EXPRESSION AND PROTEIN-PRODUCTION LEAD TO HIGH IGFBP-2 CONTENT IN MALIGNANT OVARIAN-CYST FLUID

Expression of insulin-like growth factor-I (IGF-T), its receptor and I GF-binding proteins (IGFBPs) by ovarian cancer cells and its mitogenic effect on these cells in vitro, suggest that IGF-I may have a role in regulation of human ovarian cancer. We have recently shown IGFBP-2 to be markedly elevated in malignant ovarian cyst fluid in vivo. To iden tify the origin of increased IGFBP-2 in these cyst fluids, the gene ex pression and protein content of IGFBP-2 were investigated in 14 malign ant and four benign epithelial ovarian neoplasms. IGFBP-2 mRNA was det ected in all ovarian specimens and was 2- to 30-fold higher in maligna nt than in benign neoplasms. Within the malignant tissues IGFBP-2 mRNA levels correlated with the aggressiveness of the tumour and were high er in invasive rumours than in those with borderline pathology. Southe rn blot analysis revealed no amplification of IGFBP-2 gene in the DNA samples from ovarian rumours regardless of their nature. IGFBP-2 was t he major binding protein in tissue extracts, as measured by both Weste rn ligand blotting and immunoblotting, and was significantly higher in malignant than in benign neoplasms. These findings were further suppo rted by immunohistochemical detection of IGFBP-2 in tumour sections. O ur data suggest that increased local production by the tumour in vivo is responsible for the increased IGFBP-2 levels in the cyst fluid bath ing the ovarian malignancy. This may represent an autocrine regulatory mechanism for IGF-I proliferative effect of ovarian cancer.