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 m ammary tissues and 40 breast cancer tissues, mRNA and protein expression wa s determined by quantitative reverse transcriptase-polymerase chain reactio n (RT-PCR) and immunofluorescence, mRNA levels of CD95L correlated positive ly (r=0.90;p<0.01) and transmembrane CD95 inversely (r=-0.88;p<0.01) with h istopathological 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 lo w in high-grade carcinomas, but high in benign mammary tissues, Since CD95L acts as an efficient inducer of apoptosis in CD95(+) cells, apoptotic cell s mere identified on the tissue sections. Tumourinfiltrating lymphocytes an d stromal cells in close proximity to CD95L-expressing breast cancer underw ent apoptosis. As a functional test, CD95(+) target cells were cultured on breast cancer tissue sections. The target cells underwent apoptosis when cu ltured on breast cancer sections, but could be rescued when CD95L was speci fically blocked by a CD95-Fc fusion molecule, The data suggest an inverse r egulation of CD95 ligand and receptor expression during dedifferentiation o f breast cancer. Killing of bystander cells by the CD95L-expressing breast tumour could be involved in tissue invasion. Copyright (C) 1999 John Wiley & Sons, Ltd.