N. Mitsiades et al., Fas ligand is present in tumors of the Ewing's sarcoma family and is cleaved into a soluble form by a metalloproteinase, AM J PATH, 153(6), 1998, pp. 1947-1956
Citations number
55
Categorie Soggetti
Research/Laboratory Medicine & Medical Tecnology","Medical Research Diagnosis & Treatment
Fas ligand (FasL) exists in transmembrane and soluble forms and induces apo
ptosis on cross-linking with the Fas receptor. We evaluated the biological
significance of Fast and Fas in 61 tumor tissues and 9 cell lines of the Ew
ing's sarcoma family of tumors (ESFT). Fast was present in 62.5% and Fas in
79.4% of primary ESFT, Metastatic tumors had higher expression of Fast (95
%), suggesting association with a metastatic phenotype. Fast was detected i
n the cytoplasm and membrane of ESFT cells by immunofluorescence. Western b
lotting revealed transmembrane and soluble Fast in cytosolic extracts and s
oluble Fast in conditioned media. Both transmembrane and soluble Fast induc
ed apoptosis of Fas-sensitive Jurkat cells in co-culture experiments with E
SFT cells or their media. Treatment with phenanthroline and the synthetic m
etalloproteinase inhibitor BB-3103 reduced the levels of soluble Fast in th
e media, suggesting that in ESFT, Fast is processed by a metalloproteinase
and released in the extracellular milieu. The released soluble Fast may ser
ve to attack cells of the immune system and/or interfere with the binding o
f transmembrane Fast with Fas, and results in down-regulation of transmembr
ane Fast. Synthetic metalloproteinase inhibitors may modify the ratio of tr
ansmembrane to soluble FasL.