Soluble Fas/APO-1 in tumor cells: a potential regulator of apoptosis?

• Published in: Cancer letters Vol. 94; no. 1; pp. 1 - 8
• Main Authors: Owen-Schaub, Laurie B., Angelo, Laura S., Radinsky, Robert, Ware, Carl F., Gesner, Thomas G., Bartos, David P.
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Shannon Elsevier Ireland Ltd 20-07-1995; Elsevier
• Subjects: Antigens, Surface - genetics; Antigens, Surface - physiology; Apoptosis; Apoptosis - genetics; Apoptosis - immunology; Apoptosis - physiology; Base Sequence; Biological and medical sciences; fas Receptor; Fas/APO-1; Gene Deletion; General aspects; Humans; Malignancy; Medical sciences; Molecular Sequence Data; Osteosarcoma - chemistry; Osteosarcoma - immunology; Osteosarcoma - pathology; Polymerase Chain Reaction; Soluble Fas/APO-1; T-Lymphocytes, Cytotoxic - physiology; Tumor Cells, Cultured; Tumors; Malignancy; Soluble Fas/APO-1; Apoptosis; Fas/APO-1; Human; Pathogenesis; Cytokine; Diseases of the osteoarticular system; Cytotoxicity; Monoclonal antibody; Soluble form; Malignant tumor; In vitro; Cell surface; Proteins; Tumor necrosis factor; Cell death; Osteosarcoma; Established cell line; Genetics; Bone; Mechanism of action; Tumor cell
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/0304-3835(95)03834-J

Fas/APO-1, a member of the NGF/TNF receptor superfamily expressed on the cell-surface of normal and malignant cells, is known to induce cell death by apoptosis. In the present study, we have investigated Fas/APO-1 gene defects in a human osteosarcoma cell line resistant to the apoptosis-inducing effects of anti-Fas. cDNA cloning and sequencing revealed that these cells contained both ‘authentic’ and mutant Fas/APO-1 containing a 63 base pair in-frame deletion spanning the transmembrane domain, designated DFas/APO-1. Direct evidence for the existence of a soluble Fas/APO-1 protein was obtained by immunoprecipitation and Western blotting. Taken together with prior studies demonstrating a role for Fas/APO-1 and Fas ligand, respectively, in tumor target cell killing by cytotoxic T-lymphocytes, production of soluble Fas/APO-1 might have significant implications in malignant disease pathogenesis.