CD95 ligand expression in dedifferentiated breast cancer.
CD95 ligand expression has been observed in various malignancies. Studying the CD95 ligand (CD95L) and receptor (CD95) system in eight non-malignant mammary tissues and 40 breast cancer tissues, mRNA and protein expression was determined by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and immunofluorescence. mRNA levels of CD95L correlated positively (r=0.90; p< 0.01) and transmembrane CD95 inversely (r=-0.88; p< 0.01) with histopathological grading of the breast tumours: CD95L mRNA levels were low in adenomas, but increased by 20-fold in grade I, 120-fold in grade II, and 310-fold in grade III breast cancer. In contrast, CD95 mRNA levels were low in high-grade carcinomas, but high in benign mammary tissues. Since CD95L acts as an efficient inducer of apoptosis in CD95(+) cells, apoptotic cells were identified on the tissue sections. Tumour-infiltrating lymphocytes and stromal cells in close proximity to CD95L-expressing breast cancer underwent apoptosis. As a functional test, CD95(+) target cells were cultured on breast cancer tissue sections. The target cells underwent apoptosis when cultured on breast cancer sections, but could be rescued when CD95L was specifically blocked by a CD95-Fc fusion molecule. The data suggest an inverse regulation of CD95 ligand and receptor expression during dedifferentiation of breast cancer. Killing of bystander cells by the CD95L-expressing breast tumour could be involved in tissue invasion.
Müschen
M
M
Department of Gastroenterology, Hepatology and Infectiology, Heinrich-Heine Universität, Düsseldorf, Germany.
Moers
C
C
Warskulat
U
U
Niederacher
D
D
Betz
B
B
Even
J
J
Lim
A
A
Josien
R
R
Beckmann
M W
MW
Häussinger
D
D
D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000378:metabolism*; D017209:Apoptosis; D001943:Breast Neoplasms / Q000276:immunology* / Q000473:pathology; D002454:Cell Differentiation; D053222:Fas Ligand Protein; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D019169:Jurkat Cells / Q000378:metabolism; D008024:Ligands; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019014:fas Receptor / Q000378:metabolism*
D000951:Antigens, Neoplasm; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008024:Ligands; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D019014:fas Receptor