PRODUCTION OF INSULIN-LIKE GROWTH-FACTOR BINDING-PROTEINS BY HUMAN OVARIAN-CARCINOMA CELLS

Cells of the human ovarian carcinoma lines EFO-21, EFO-27, MFO-35 and MFO-36 secrete binding proteins for insulin-like growth factors (IGFBP s) into their culture media. By sodium dodecyl sulfate/polyacrylamide gel electrophoresis (SDS-PAGE) and ligand blotting, seven groups of IG FBPs with molecular masses of 25, 30 (doublet), 34, 37, 40, 45, and 50 kDa were observed, depending on the cell line under investigation. By Northern blot analyses using cDNAs or oligonucleotides specific for t he six types of IGFBP (IGFBP-1 to IGFBP-6), mRNA for all IGFBPs tested except for IGFBP-1 could be detected in the ovarian carcinoma cell ex tracts. In detail, analysis of EFO-21 protein products by SDS-PAGE yie lded IGFBPs of 25, 34, and 50 kDa; extracts of EFO-21 cells contained mRNAs for IGFBP-2, -3, -4, and -6. EFO-27 cells produced IGFBPs of 40 kDa and 45 kDa as determined by SDS-PAGE, and mRNAs for IGFBP-3, -4, a nd -6 were detected. In the conditioned medium of MFO-35 cells, IGFBPs of 25, 30 (doublet), 34, 37, 40, and 45 kDa were observed by SDS-PAGE , while mRNAs for the five proteins IGFBP-2 to IGFBP-6 were found. MFO -36 cells produced IGFBPs of 34 kDa and 50 kDa as determined by SDS-PA GE, and the cells expressed mRNAs for IGFBP-2, -3, -4, and -6. In rela tion to published molecular mass data of the known IGFBPs, the size of the secreted proteins could be correlated to the mRNA patterns expres sed by the ovarian carcinoma cells. It is concluded that ovarian carci noma cells frequently express IGFBP-3, -4, and -6 and, to a lesser ext ent, IGFBP-2; the expression of IGFBP-5 appears as a rather rare event , while IGFBP-1 was not found to be expressed in ovarian carcinoma cel ls.