title: Assessment of CAR- or CD46-dependent adenoviral vector-mediated TRAIL gene therapy in clinical adenocarcinoma lung cancer cells.
abstract: Adenoviral vector-mediated transfer of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can be a powerful approach to lung cancer therapy. However, the efficiency of adenoviral vector gene transfer and the sensitivity to TRAIL-induced apoptosis in the context of adenoviral vector gene transfer have yet to be characterized in primary lung cancers. In this study, we investigated the expression of adenoviral receptor CD46 expression in primary lung cancer cells. In contrast to previous reports on enhanced CD46 expression in various types of cancer cells, we show a significantly higher CD46 expression in lung adenocarcinomas compared to lung squamous cell carcinomas. Using Ad5-GFP and Ad5F35-GFP vectors, we demonstrated an improved gene transfer efficiency in primary lung cancer cells by the Ad5F35 vector. The apoptosis induction effect mediated by Ad5-TRAIL and Ad5F35-TRAIL vector gene transfer was compared in cells from 10 lung adenocarcinomas. Of 5 lung cancers in which apoptosis was induced, 2 had an enhanced effect by Ad5F35-TRAIL vector gene transfer compared to Ad5-GFP. Thus, these results indicate a method to identify TRAIL-sensitive primary lung cancers, which will also facilitate the analysis of resistance mechanisms in lung cancers.
authors.affiliation: Laboratory Center, Changzhou Second Hospital, Nanjing Medical University, Jiangsu, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Wang
authors.forename: Lingdi
authors.initials: L
authors.lastname: Ma
authors.forename: Shizhong
authors.initials: S
authors.lastname: Wang
authors.forename: Yongyi
authors.initials: Y
authors.lastname: Bao
authors.forename: Cheng
authors.initials: C
authors.lastname: Ni
authors.forename: Naifu
authors.initials: N
authors.lastname: Guan
authors.forename: Jianzhong
authors.initials: J
authors.lastname: Zhao
authors.forename: Xiaolong
authors.initials: X
authors.lastname: Fan
mesh_terms: D000230:Adenocarcinoma / Q000628:therapy*; D000256:Adenoviridae / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D045744:Cell Line, Tumor; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D005260:Female; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D008175:Lung Neoplasms / Q000628:therapy*; D008297:Male; D051916:Membrane Cofactor Protein / Q000502:physiology*; D008875:Middle Aged; D011991:Receptors, Virus / Q000502:physiology*; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics*
chemical_list: C497857:CD46 protein, human; C568771:CLMP protein, human; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D051916:Membrane Cofactor Protein; D011991:Receptors, Virus; D053221:TNF-Related Apoptosis-Inducing Ligand