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Treatment of choriocarcinoma cells with differentiation-inducing agents modulates their adhesive and invasive properties
A.44
Placenta (1993), Vol 14
TREATMENT OF CHORIOCARCINOMA CELLS WITH DIFFERENTIATIONINDUCING A G E N T S MODULATES THEIR ADHESIVE AND INVASIVE
PROPERTIES. M. Linke, H.-P. Hohn, H..W. Denker, Institute of Anatomy, Hospital, D-45122 Essen (FRG)
University
During implantation and placentation trophoblast cells undergo a complex differentiation program in preparation for their various functions in the course of gestation: adhesive and invasive interactions with the endometrial epithelium and stroma, production of pregnancyspecific hormones and transport of nutrients. We are studying how adhesiveness and invasiveness of human trophoblastic cells are correlated with cell differentiation in vitro using choriocarcinoma cells as a model. Cells (BeWo, JAr, JEG-3) were treated with chemical modulators of differentiation: retinoic acid (RA), methotrexate (MTX), dibutyryl cyclic AMP (cAMP) and phorbol-12-myristoyl-13-acetate (PMA). Differentiation was then monitored by measuring the secretion of chorionic gonadotropin (hCG). Adhesive behaviour was tested in two systems: (i) cell-cell-adhesion of multicellular choriocarcinoma spheroids to monolayers of the endometrial cell line RL95-2; (ii) cell-matrix-adhesion of suspended single cells to isolated components of the ECM (fibronectin, laminin, collagen I and IV) and to the complex basement membrane-like matrix Matrigel. Invasiveness was measured in a Transwell chamber assay where cells have to penetrate Matrigel-coated filters (pore size 8 I~m). The tested modulators stimulated differentiation in terms of increased secretion of hCG in all three cell lines. Adhesion to endometrial cells was always reduced but to varying degrees up to total inhibition of attachment. In contrast, adhesion to ECM components was not much altered. Invasion was affected heterogeneously: RA and PMA increased, MTX and cAMP decreased invasiveness of JAr cells. These results suggest an inverse correlation between differentiation and cell-cell-adhesion of choriocarcinoma cells. The relation between differentiation and invasion appears to be more complex, possibly depending on the pathway of signal transduction that is influenced by these effectors of differentiation. Supportedby the Dr.-Mildreed-Scheel-Stiftungfdr Krebsforschung.
STEREOLOGICAL STUDY OF THE PLACENTAE IN INTRAUTERINE GROWTH RETARDATION ~ITH DIFFERENT PONDERAL INDEX. Bo Ning Liu and Wen Oi Tao. Pathology Research Lab. , I)B/GYN Dept. Shanghai 6th People's Il o sp it a l, Shanghai 2OO233,P.R.China. IO placentae each from the oases of IUGR with normal ponderal index (NPI) and low ponderal index (LP1) and lO from normal pregnancy as control were analysed q u a n t i t a t i v e l y with stereological p r i n c i p l e s . This study showed the placental weight, volume, surface area of v i l l i and v i l l o u s f e t a l c a p i l l a r y in IUGR were s i g n i f i c a n t l y reduced than that in control group. The percentage r a t i o of the fetal c a p i l l a r y volume was increased s i g n i f i c a n t l y in IUGR group but the r a t i o of vasculo -synoytial membrane/villous f e t a l c a p i l l a r y decreased. And the other lO placentas of IUGR were provided for investigation at the u l t r a s t r u c t u r a l level to estimate the a i c r o v i l l o u s and i n t e r ~ i e r o v i l l o u s surface densities. The data showed the intermierovillous surface density in IUGR was s i g n i f i c e n t l y reduced than that in control group, l t suggested that compensation to anoxemia in placenta of IUGR was incomplete. The data also found that a l l the parameters in NPI group were decreased s i g n i f i o a n l y than that in LP! group, which implied NPI group had a more severe growth deficiency of the placental functional structure. ~hen placental growth deficiency occurs in the f i r s t or second trimester,both the f e t a l length and weight w i l l be severely affected.
Placenta (1993), Vol 14
TREATMENT OF CHORIOCARCINOMA CELLS WITH DIFFERENTIATIONINDUCING A G E N T S MODULATES THEIR ADHESIVE AND INVASIVE
PROPERTIES. M. Linke, H.-P. Hohn, H..W. Denker, Institute of Anatomy, Hospital, D-45122 Essen (FRG)
University
During implantation and placentation trophoblast cells undergo a complex differentiation program in preparation for their various functions in the course of gestation: adhesive and invasive interactions with the endometrial epithelium and stroma, production of pregnancyspecific hormones and transport of nutrients. We are studying how adhesiveness and invasiveness of human trophoblastic cells are correlated with cell differentiation in vitro using choriocarcinoma cells as a model. Cells (BeWo, JAr, JEG-3) were treated with chemical modulators of differentiation: retinoic acid (RA), methotrexate (MTX), dibutyryl cyclic AMP (cAMP) and phorbol-12-myristoyl-13-acetate (PMA). Differentiation was then monitored by measuring the secretion of chorionic gonadotropin (hCG). Adhesive behaviour was tested in two systems: (i) cell-cell-adhesion of multicellular choriocarcinoma spheroids to monolayers of the endometrial cell line RL95-2; (ii) cell-matrix-adhesion of suspended single cells to isolated components of the ECM (fibronectin, laminin, collagen I and IV) and to the complex basement membrane-like matrix Matrigel. Invasiveness was measured in a Transwell chamber assay where cells have to penetrate Matrigel-coated filters (pore size 8 I~m). The tested modulators stimulated differentiation in terms of increased secretion of hCG in all three cell lines. Adhesion to endometrial cells was always reduced but to varying degrees up to total inhibition of attachment. In contrast, adhesion to ECM components was not much altered. Invasion was affected heterogeneously: RA and PMA increased, MTX and cAMP decreased invasiveness of JAr cells. These results suggest an inverse correlation between differentiation and cell-cell-adhesion of choriocarcinoma cells. The relation between differentiation and invasion appears to be more complex, possibly depending on the pathway of signal transduction that is influenced by these effectors of differentiation. Supportedby the Dr.-Mildreed-Scheel-Stiftungfdr Krebsforschung.
STEREOLOGICAL STUDY OF THE PLACENTAE IN INTRAUTERINE GROWTH RETARDATION ~ITH DIFFERENT PONDERAL INDEX. Bo Ning Liu and Wen Oi Tao. Pathology Research Lab. , I)B/GYN Dept. Shanghai 6th People's Il o sp it a l, Shanghai 2OO233,P.R.China. IO placentae each from the oases of IUGR with normal ponderal index (NPI) and low ponderal index (LP1) and lO from normal pregnancy as control were analysed q u a n t i t a t i v e l y with stereological p r i n c i p l e s . This study showed the placental weight, volume, surface area of v i l l i and v i l l o u s f e t a l c a p i l l a r y in IUGR were s i g n i f i c a n t l y reduced than that in control group. The percentage r a t i o of the fetal c a p i l l a r y volume was increased s i g n i f i c a n t l y in IUGR group but the r a t i o of vasculo -synoytial membrane/villous f e t a l c a p i l l a r y decreased. And the other lO placentas of IUGR were provided for investigation at the u l t r a s t r u c t u r a l level to estimate the a i c r o v i l l o u s and i n t e r ~ i e r o v i l l o u s surface densities. The data showed the intermierovillous surface density in IUGR was s i g n i f i c e n t l y reduced than that in control group, l t suggested that compensation to anoxemia in placenta of IUGR was incomplete. The data also found that a l l the parameters in NPI group were decreased s i g n i f i o a n l y than that in LP! group, which implied NPI group had a more severe growth deficiency of the placental functional structure. ~hen placental growth deficiency occurs in the f i r s t or second trimester,both the f e t a l length and weight w i l l be severely affected.