CD95 ligand expression in dedifferentiated breast cancer

Autor: M, Müschen, C, Moers, U, Warskulat, D, Niederacher, B, Betz, J, Even, A, Lim, R, Josien, M W, Beckmann, D, Häussinger
Rok vydání: 1999
Předmět:
Zdroj: The Journal of pathology. 189(3)
ISSN: 0022-3417
Popis: 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; p0.01) and transmembrane CD95 inversely (r=-0.88; p0.01) 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.
Databáze: OpenAIRE