BIOLOGICAL-ACTIVITY OF THE RECEPTOR FOR MACROPHAGE-COLONY-STIMULATINGFACTOR IN THE HUMAN ENDOMETRIAL CANCER CELL-LINE, ISHIKAWA

Previously we found that the Ishikawa endometrial cancer cell line exp resses macrophase colony-stimulating factor (M-CSF) and c-fms transcri pts and that its proliferation is enhanced by the addition of recombin ant M-CSF. This suggested that Ishikawa cells are constitutively stimu lated by M-CSF. In support of this we now show that Ishikawa cells sec rete 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-Sms genes in Ishikawa cells we also demonstrate proliferation to be partially inhibited by a dominant negative, mutant c-fms gene, yet enhanced approximately 3-f old 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 c ancer cells and suggests the possibility of such activity in tumours o f the endometrium and ovary that aberrantly express M-CSF and fms gene s.