Is Stat3 activation in trophoblast cells required for invasiveness ?



OBJECTIVES:  Phosphorylation and dimerization of Stat3 (Signal Transducer and Activator of Tran- scription 3) is related to the malignancy of tumor cells and potentially to their invasive properties. Extravillous trophoblast cells resemble cancer cells in this aspect since they invade decidual tissue, although only up to a well-regulated limit. We aim to investigate the contribution of Stat3 to this phenomenon.

METHODS:  Extravillous trophoblast cells were isolated from human term placentae by mechanical and enzymatic tissue disaggregation, density gradient and magnet-activated cell separation (MACS). Stat3 expression and tyrosine phosphorylation were studied by Western blot analysis, specific DNA-binding activity of Stat3 was tested by an electrophoretic mobility shift assay (EMSA). For comparison, various tumor cells were investigated.

RESULTS:  Trophoblast cells from term placentae express Stat3, which is inactive in native ex vivo cells. In contrast, cells from various invasive tumors display a high rate of activated Stat3. Currently, first trimester trophoblast and choriocarcinoma cells are studied in order to correlate their state of Stat3 expression/ activation with their degree of invasiveness.

CONCLUSION:  The presence of Stat3 in trophoblast cells implicates its stimulatability, which might be related to their invasive phenotype. The lack of tyrosine phosphorylation of Stat3 in term tropho- blast cells might be due to their resting, non-invasive status.