Differentiation Markers and Invasiveness: Discordant Regulation in Normal Trophoblast and Choriocarcinoma Cells

In tumor cells, malignant (invasive) behavior and differentiation tend to be correlated inversely, although it is not clear to what extent this can be generalized and whether it may also apply to normal invasive cell types. We have modulated differentiation of normal trophoblast cells from first trimester or term placenta as well as choriocarcinoma cells (BeWo, Jeg-3, and JAr) with retinoic acid (RA), methotrexate (MTX), dibutyryl-cAMP (dbcAMP), or phorbol-[12-myristoyl-13-acetyl]-diester (PMA). The secretion of the differentiation marker chorionic gonadotrophin was stimulated by nearly all substances in all cell types. The activity of cellular sterylsulfatase showed a tendency to be increased (decreased by RA and dbcAMP in normal trophoblast; not detected in JAr). Invasiveness was decreased by all effectors in normal trophoblast (both types) and in BeWo. In Jeg-3 and JAr, however, PMA treatment (in JAr also RA treatment) increased invasion rates. These results suggest that only in normal trophoblast and in BeWo (but not in other choriocarcinoma cells, i.e., Jeg-3 and JAr) invasiveness and differentiation tend to be correlated inversely. When extrapolating to the various subpopulations of cells within a tumor, induction of differentiation-as intended in certain strategies for tumor therapy ("differentiation therapy")-may have the unwanted effect of stimulating invasiveness in certain subpopulations of tumor cells.