MACROPHAGE-COLONY-STIMULATING FACTOR IS EXPRESSED BY AN OVARIAN-CARCINOMA SUBLINE AND STIMULATES THE C-MYC PROTOONCOGENE

A small, fast-growing and non-differentiated clone (N.1) derived from the heterogeneous human epithelial ovarian carcinoma cell line HOC-7 p roduces an autocrine/paracrine factor that is secreted into the cell c ulture supernatant. This factor is capable of enhancing mRNA levels of the proliferation-related oncogene c-myc in the more differentiated c lone D3 and in normal human fibroblasts MRC.5, but also in N.1 cells t hemselves. Supernatants enriched for this paracrine/autocrine factor a lso confer a mitogenic stimulus as measured by [H-3]thymidine incorpor ation. Trypsin can neutralise the stimulating activity of the secreted factor as well as monoclonal antibodies directed against macrophage c olony-stimulating factor (M-CSF). We show that M-CSF and also M-CSF re ceptor are expressed in N.1 cells and that recombinant M-CSF induces c -myc transcript levels in N.1 cells. This investigation raises the pos sibility that M-CSF might be an autocrine growth factor in non-differe ntiated ovarian carcinomas. Inappropriate cytokine production could cr eate a tumour-promoting microenvironment in this cancer type.