Biological activity of the receptor for macrophage colony-stimulating factor in the human endometrial cancer cell line, Ishikawa.

Previously we found that the Ishikawa endometrial cancer cell line expresses macrophage colony-stimulating factor (M-CSF) and c-fms transcripts and that its proliferation is enhanced by the addition of recombinant M-CSF. This suggested that Ishikawa cells are constitutively stimulated by M-CSF. In support of this we now show that Ishikawa cells secrete M-CSF and that known stimulators of M-CSF production increase the amount detected in Ishikawa cell conditioned medium. Using retroviral infections to introduce and express exogenous c-fms genes in Ishikawa cells we also demonstrate proliferation to be partially inhibited by a dominant negative, mutant c-fms gene, yet enhanced approximately 3-fold by a normal c-fms gene, under conditions in which the only source of M-CSF was that produced by the cells. The data provide evidence for the existence of an active M-CSF/receptor loop in these endometrial cancer cells and suggests the possibility of such activity in tumours of the endometrium and ovary that aberrantly express M-CSF and fms genes.