Assessment of CAR- or CD46-Dependent Adenoviral Vector-Mediated TRAIL Gene Therapy in Clinical Adenocarcinoma Lung Cancer Cells

• 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. Copyright (C) 2010 S. Karger AG, Basel

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)

Nyckelord

apoptosis-inducing ligand

Tumor necrosis factor-related

Apoptosis

Lung cancer

Gene therapy

Publikations- och innehållstyp

art (ämneskategori)

ref (ämneskategori)