CD95 ligand expression in dedifferentiated breast cancer

CD95 ligand expression has been observed in various malignancies. Studying the CD95 ligand (CD95L) and receptor (C95) system in benign and malignant breast tumours from 48 patients mRNA and protein expression were determined by quantitative RT-PCR and immunofluorescence. mRNA levels of CD95 correlated inversely (r = 0.90; P <0.01) and CD95L positively (r = 0.89; P <0.01) with histopathological grading of the breast tumours. CD95 mRNA levels were low in high-grade carcinomas, but high in benign mammary tissues. In contrast, CD95 mRNA levels were low in adenomas, but increased 20-fold in grade I, 120-fold in grade II and 310-fold in grad III breast cancer.

Since CD95L acts as an efficient inducer of apoptosis in CD95+ cells, apoptotic cells were identified on the tissue sections. Tumour infiltrating lymphocytes and stroma cells in close proximity to CD95L expressing breast cancer underwent apoptosis. As a functional test, CD95 + target cells were cultured on breast cancer 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.

In conclusion, the findings suggest an inverse regulation of CD95 and CD95L expression during dedifferentation of breast cancer and that killing of bystander cells by the CD95L expressing tumour could be involved in tissue invasion.