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 t his can be generalized and whether it may also apply to normal invasiv e 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 (M TX), dibutyryl-cAMP (dbcAMP), or phorbol-[12-myristoyl-13-acetyl]-dies ter (PMA). The secretion of the differentiation marker chorionic gonad otrophin was stimulated by nearly all substances in all cell types. Th e activity of cellular sterylsulfatase showed a tendency to be increas ed (decreased by RA and dbcAMP in normal trophoblast; not detected in JAr). Invasiveness was decreased by all effecters in normal trophoblas t (both types) and in BeWo. In Jeg-3 and JAr, however, PMA treatment ( in JAr also RA treatment) increased invasion rates. These results sugg est that only in normal trophoblast and in BeWo (but not in other chor iocarcinoma cells, i.e., Jeg-3 and JAr) invasiveness and differentiati on tend to be correlated inversely. When extrapolating to the various subpopulations of cells within a tumor, induction of differentiation-a s intended in certain strategies for tumor therapy (''differentiation therapy'')-may have the unwanted effect of stimulating invasiveness in certain subpopulations of tumor cells. (C) 1998 Academic Press.