Expression of functional Fas ligand in choriocarcinoma.
OBJECTIVE
In the course of pregnancy, fetal trophoblast cells and in that of choriocarcinoma-etiology, trophoblast derived tumor cells, invade the uterine mucosa without causing rejection by decidual leukocytes. Fas ligand (FasL, CD95L, APO-IL), a central regulator of the immune system, has been implicated in the maintenance of immune privileged sites, such as the eye, the testis and the pregnant uterus by inducing apoptosis in activated infiltrating leukocytes. In normal pregnancy FasL, which is expressed by trophoblast cells, appears to contribute to the immune privilege of the pregnant uterus. As choriocarcinoma derives from trophoblast we wanted to assess the expression of FasL in this tissue.


METHODS
Immunohistochemistry, immunofluorescence, TUNEL-assay, Western blotting, coculture experiments and flourescence-associated cell sorter-analysis were the techniques used.


RESULTS
Expression of FasL was found on cells of choriocarcinoma in paraffin sections in situ and on three choriocarcinoma cell lines such as JEG-3, JAR and BeWo. These results were confirmed by Western blotting. In coculture experiments choriocarcinoma cells induced apoptosis in a Jurkat cell line - sensitive to FasL mediated killing. However, when the Jurkat cells were pre-incubated with a Fas-blocking monoclonal antibody, apoptosis was abolished to a great extent.


CONCLUSIONS
Our findings show that choriocarcinoma cells express FasL and this aforementioned molecule is biologically active. We assume that FasL expression on choriocarcinoma cells may contribute to control of anti-tumor responses by inducing apoptosis in activated Fas bearing leukocytes.
Hammer
Astrid
A
Institute of Histology and Embryology, Karl-Franzens-University, Graz, Austria. astrid.hammer@kfunigraz.ac.at
Hartmann
Michaele
M
Sedlmayr
Peter
P
Walcher
Wolfgang
W
Kohnen
Gaby
G
Dohr
Gottfried
G
D000328:Adult; D000906:Antibodies / Q000276:immunology; D017209:Apoptosis / Q000276:immunology; D015153:Blotting, Western; D002822:Choriocarcinoma / Q000276:immunology / Q000378:metabolism*; D018920:Coculture Techniques; D053222:Fas Ligand Protein; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D019169:Jurkat Cells / Q000276:immunology / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology; D011247:Pregnancy; D014594:Uterine Neoplasms / Q000378:metabolism
D000906:Antibodies; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins