title: Expression of TRAIL (TNF-related apoptosis-inducing ligand) and its receptors in normal colonic mucosa, adenomas, and carcinomas.
abstract: Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis in tumour cell lines. Four membrane-bound receptors for TRAIL have been identified, two apoptosis-mediating receptors, DR4 and DR5, and two apoptosis-inhibiting receptors, DcR1 and DcR2. The aim of this study was to examine the role of TRAIL and its receptors in colorectal cancer development. The immunohistochemical expression and localization of TRAIL and its receptors were investigated in normal mucosa (n=10), adenomas (n=19), and carcinomas (n=21). Correlations between the expression of TRAIL and its receptors and the degree of apoptosis (assessed by M30 expression) and histopathological characteristics were explored. TRAIL and its receptors were expressed in normal mucosal epithelium. Expression of the receptors was seen in adenomas and carcinomas. TRAIL expression was lost in a subset of colorectal tumours, more frequently in carcinomas than in adenomas (p<0.05). DR4 and DR5 staining was stronger in neoplastic cells than in normal cells and was accompanied by a higher degree of apoptosis. No differences were found between tumour and normal cells regarding DcR1 and DcR2 expression. No correlations were found between TRAIL or TRAIL receptor expression and histopathological characteristics. In conclusion, marked changes were seen in the course of the adenoma-carcinoma sequence with respect to the expression of TRAIL and TRAIL receptors DR4 and DR5. The stronger expression of DR4 and DR5 in neoplastic cells than in normal cells, together with a higher degree of apoptosis, suggests a possible functional role for these receptors in apoptosis induction in neoplastic colorectal cells.
authors.affiliation: Department of Medical Oncology, University Hospital, Groningen, The Netherlands.
authors.forename: Jan J
authors.initials: JJ
authors.lastname: Koornstra
authors.forename: Jan H
authors.initials: JH
authors.lastname: Kleibeuker
authors.forename: Caroline M M
authors.initials: CM
authors.lastname: van Geelen
authors.forename: Fleur E M
authors.initials: FE
authors.lastname: Rijcken
authors.forename: Harry
authors.initials: H
authors.lastname: Hollema
authors.forename: Elisabeth G E
authors.initials: EG
authors.lastname: de Vries
authors.forename: Steven
authors.initials: S
authors.lastname: de Jong
mesh_terms: D000236:Adenoma / Q000378:metabolism / Q000503:physiopathology*; D015703:Antigens, CD / Q000032:analysis; D000951:Antigens, Neoplasm / Q000032:analysis; D000970:Antineoplastic Agents / Q000032:analysis*; D017209:Apoptosis / Q000502:physiology; D051017:Apoptosis Regulatory Proteins; D015153:Blotting, Western; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000503:physiopathology*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007413:Intestinal Mucosa / Q000378:metabolism; D008024:Ligands; D008562:Membrane Glycoproteins / Q000032:analysis*; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor / Q000032:analysis; D053221:TNF-Related Apoptosis-Inducing Ligand; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis*; D019014:fas Receptor / Q000032:analysis
chemical_list: D015703:Antigens, CD; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D008024:Ligands; D008562:Membrane Glycoproteins; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor; D053221:TNF-Related Apoptosis-Inducing Ligand; C105190:TNFRSF10A protein, human; C505639:TNFRSF10B protein, human; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor