Coxsackie B and adenovirus receptor, integrin and major histocompatibility complex class I expression in human prostate cancer cell lines: implications for gene therapy strategies

Abstract

Gene therapy strategies based on modifying tumour cells using high efficiency adenoviral vectors have shown promise in the clinic. Recently the Coxsackie and adenovirus receptor (CAR) has been shown to mediate adenoviral entry into tumour cells, although previous studies also suggested a role for MHC class I heavy chain. Detailed evaluation of the expression of both CAR and MHC class I in prostate cancer cell lines would have important implications for therapeutic strategies. We have found that, unlike cell lines derived from other malignancies, in human and murine prostate cancer loss of CAR expression appears to be relatively infrequent and does not correlate with loss of MHC class I expression. These findings, together with the demonstration of appreciable levels of cellsurface expression of integrins, suggest that cancer vaccine strategies based on modifying whole prostate cancer cells should be feasible using the current generation of recombinant adenoviral vectors, without deleterious effects on either the virus vector or the target cell.

Histone deacetylase inhibitor trichostatin A enhances the antitumor effect of the oncolytic adenovirus H101 on esophageal squamous cell carcinoma in vitro and in vivo

“…It has become apparent that a major determinant of Ads-mediated gene transfer efficacy is the expression of its primary receptor, CAR, on target cells (47). In order to infect tumor cells efficiently, H101 requires CAR for attachment and α v integrin for internalization (48). In the present study, the expression levels of CAR in the mouse xenograft tumor tissue were increased in the TSA group, and in the TSA and H101 combination group.…”

Enhanced delivery of mda-7/IL-24 using a serotype chimeric adenovirus (Ad.5/3) improves therapeutic efficacy in low CAR prostate cancer cells

“…The infectivity of Ad on different prostate cancer cells has been previously analyzed. 34,35 DU-145 and LNCaP have high CAR, whereas PC-3 has lower cell-surface CAR, which makes it relatively resistant to Ad infection. To circumvent this viral resistance, genetically engineered PC-3 cells have been generated by increasing 35% of CAR-positive cells to 86% CAR-positive cells.…”

The roles of cell surface attachment molecules and coagulation Factor X in adenovirus 5-mediated gene transfer in pancreatic cancer cells

“…Previous investigations on the relative importance of cell surface attachment molecules have shown that CAR expression appears to regulate cell susceptibility to Ad5 transduction much more significantly than a v -integrin expression in a wide range of primary cells and established cell lines. [28][29][30][31][32] However, another report has suggested that transgene expression in Ad5-transduced lung and pancreatic cancer cell lines correlated with levels of b 3 integrin. 20 Furthermore, it has recently been proposed that when cell surface CAR levels are low, a v b 5 can function as an attachment molecule for Ad5 in melanoma and breast cancer cell lines.…”