Functional expression of TRAIL receptors TRAIL-R1 and TRAIL-R2 in esophageal adenocarcinoma.

Abstract

The tumour necrosis factor (TNF) related apoptosis-inducing ligand (TRAIL/Apo2L) is a member of the TNF superfamily that preferentially induces apoptosis in cancer cells, while sparing normal cells. TRAIL induces apoptosis by interacting with its receptors TRAIL-R1 and TRAIL-R2. Recently, new humanized agonistic anti-TRAIL-R1 and anti-TRAIL-R2 antibodies have been developed, and are undergoing phase I/II clinical trails. Esophageal adenocarcinoma (EA) is associated with significantly poor outcome and is rapidly increasing in incidence in the United States and Western Europe, with virtually no effective non-surgical treatment. The aim of this study was to determine whether human EA tissue express TRAIL-R1 and/or TRAIL-R2, and whether EA cell lines Bic-1 and Seg-1 expresses functional TRAIL-R1 and/or TRAIL-R2. The expression of TRAIL-R1 and TRAIL-R2 was determined in sections from 18 human EA by immunohistochemistry (IHC). Sixteen (89%) of the EA expressed TRAIL-R1 and 17 (94%) expressed TRAIL-R2. Both cell lines were found to express TRAIL-R1 and TRAIL-R2 by western blot analysis, IHC, and flow cytometry. The fully human agonistic TRAIL-R1 (HGS-ETR1) and TRAIL-R2 (HGS-ETR2) antibodies induced apoptosis in Bic-1 and Seg-1 cells in a time and dose dependent manner. Our results show that the vast majority of primary human EA express TRAIL-R1 and TRAIL-R2 and that EA cells lines express functional TRAIL-R1 and TRAIL-R2. Targeting of these receptors by agonist monoclonal antibodies may be of therapeutic value in patients with EA.

• Authors: Mamoun Younes, Georgios V Georgakis, Mahdis Rahmani, David Beer, Anas Younes
• Journal: European journal of cancer (Oxford, England : 1990) (Eur J Cancer) Vol. 42 Issue 4 Pg. 542-7 (Mar 2006) ISSN: 0959-8049 [Print] England
• PMID: 16426839 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Antibodies
• Receptors, TNF-Related Apoptosis-Inducing Ligand
• Receptors, Tumor Necrosis Factor
• TNFRSF10A protein, human
• TNFRSF10B protein, human

Topics

• Adenocarcinoma (metabolism, pathology)
• Adult
• Aged
• Aged, 80 and over
• Antibodies (pharmacology)
• Apoptosis (immunology)
• Cell Line, Tumor
• Esophageal Neoplasms (metabolism, pathology)
• Flow Cytometry
• Humans
• Immunohistochemistry
• Male
• Middle Aged
• Receptors, TNF-Related Apoptosis-Inducing Ligand
• Receptors, Tumor Necrosis Factor (immunology, metabolism)