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Published on: September 20, 2016
Coxsackievirus and adenovirus receptor expression in non-malignant lung tissues and clinical lung cancers
Yong Wang1, Shizhong Wang, Yongyi Bao
1Changzhou Second Hospital, Nanjing Medical University, Jiangsu, China.
Abstract:
Adenoviral vector mediated gene delivery has been applied in clinical trials and mechanistic studies to explore new treatment approaches for lung cancers. The expression of coxsackievirus adenovirus receptor (CAR), the primary receptor for the most commonly used adenovirus serotype 5 (Ad5)-based vectors, predominantly determines the permissiveness of lung cancer cells. CAR expression is also suggested to modulate tumor cell proliferation capacity. Here, we studied CAR expression in archival lung cancer specimens by using well-characterized CAR 72 antibodies. High levels of CAR expression were observed in most of the 32 cases of squamous cell carcinoma lung cancers and in all the five cases of small cell lung cancers investigated. In contrast, high levels of CAR expression were detected only in 6 of 22 adenocarcinoma lung cancers. The relative levels of CAR expression did not correlate with the pathologic grade in lung cancers, and was thus inconsistent with a role of modulating cancer cell proliferation. Of note, CAR expression was not detected in non-malignant alveolar cells. Our data suggest a preferred utility of Ad5 vector mediated gene delivery to squamous cell carcinoma lung cancers, small cell lung cancers, but not to the majority of adenocarcinoma lung cancers.
Insights
Adenovirus serotype 5 (Ad5) vectors target lung cancers by binding to the coxsackievirus adenovirus receptor (CAR). High CAR expression in squamous cell and small cell lung cancers suggests Ad5 utility, unlike most adenocarcinomas.
Area of Science:
- Oncology
- Gene Therapy
- Molecular Biology
Background:
- Adenoviral vector gene delivery shows promise for lung cancer treatment.
- Adenovirus serotype 5 (Ad5) vectors utilize the coxsackievirus adenovirus receptor (CAR) for cell entry.
- CAR expression levels influence lung cancer cell permissiveness and potentially proliferation.
Purpose of the Study:
- To investigate coxsackievirus adenovirus receptor (CAR) expression in various lung cancer subtypes.
- To determine the correlation between CAR expression and clinicopathological features.
- To assess the potential utility of Ad5-based vectors for gene delivery in different lung cancer types.
Main Methods:
- Analysis of archival lung cancer specimens.
- Immunohistochemical detection of CAR expression using CAR 72 antibodies.
- Correlation of CAR levels with lung cancer histology (squamous cell, small cell, adenocarcinoma) and grade.
Main Results:
- High CAR expression was prevalent in squamous cell (32/32) and small cell (5/5) lung cancers.
- Adenocarcinoma lung cancers showed variable CAR expression, with high levels in only 6 of 22 cases.
- CAR expression did not correlate with tumor grade and was absent in non-malignant alveolar cells.
Conclusions:
- Adenovirus serotype 5 (Ad5) vectors demonstrate potential for gene delivery in squamous cell and small cell lung cancers due to high CAR expression.
- The majority of adenocarcinoma lung cancers may not be suitable for Ad5 vector-mediated gene delivery because of low CAR expression.
- CAR expression levels are a critical factor in determining the efficacy of Ad5-based gene therapy for specific lung cancer subtypes.
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