Macrophage colony-stimulating factor is expressed by an ovarian carcinoma subline and stimulates the c-myc proto-oncogene

Abstract

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