EFFECT OF LEUKEMIA INHIBITORY FACTOR ON HUMAN CYTOTROPHOBLAST DIFFERENTIATION ALONG THE INVASIVE PATHWAY

PROBLEM: Leukemia inhibitory factor (LIF) is a pleiotropic secreted cytokine that was shown to be essential for blastocyst implantation in mice. Since it is well documented that LIF is produced by the human endometrium, we wondered if this cytokine was capable of modulating the invasive behaviour of human cytotrophoblastic cells (CTB). METHODS: CTB were isolated and purified from first trimester abortions, separated or not into cells bearing a laminin or a fibronectin receptor (alpha 6 beta 4 or alpha 5 beta 1 respectively) using specific monoclonal antibodies and magnetic particles. RESULTS: We observed that rhLIF inhibited the secretion of gelatinases and of hCG by CTB but remained without effects on the secretion of fetal fibronectin (fFN). These effects were exerted on different CTB subsets: although rhLIF inhibited the secretion of gelatinases by alpha 6 positive cells, it stimulated the fFN secretion by alpha 5 positive cells. The inhibitory effect of rhLIF on the secretion of hCG was mainly due to its effect on the hCG secretion of alpha 5 positive CTB. CONCLUSIONS: Taken together these results suggest that in vitro LIF inhibits the differ entiation of CTB towards an invasive phenotype by inhibiting the secretion of metalloproteinases, by increasing the deposition of fFN into the extracellular matrix and by inhibiting the differentiation of CTB into syncytium.