title: The roles of cell surface attachment molecules and coagulation Factor X in adenovirus 5-mediated gene transfer in pancreatic cancer cells.
abstract: Transduction of 11 pancreatic cancer cell lines with a replication-deficient adenovirus 5 expressing enhanced green fluorescent protein (Ad5EGFP) was analyzed and variable EGFP levels were observed, ranging from <1% to ∼40% of cells transduced, depending on the cell line. Efficient Ad5EGFP transduction was associated mainly with higher levels of cell surface Coxsackie and adenovirus receptor (CAR) but not with expression of α(v)β(3) and α(v)β(5) integrins and was fiber dependent. Reduction of CAR by RNA interference resulted in a corresponding decrease in Ad5EGFP transduction. Pre-treatment of Ad5EGFP with blood coagulation Factor X increased virus entry even in the presence of low CAR levels generated by RNA interference, suggesting a potential alternative route of Ad5 entry into pancreatic cancer cells. Immunohistochemistry carried out on 188 pancreatic ductal adenocarcinomas and 68 matched controls showed that CAR was absent in 102 (54%) of adenocarcinomas, whereas moderate and strong staining was observed in 58 (31%) and 28 (15%) cases, respectively. Weak or absent CAR immunolabeling correlated with poor histological differentiation of pancreatic cancer. In normal tissue, strong immunolabeling was detected in islet cells and in the majority of inter- and intralobular pancreatic ducts.
authors.affiliation: Institute of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, UK.
authors.forename: S
authors.initials: S
authors.lastname: Hamdan
authors.forename: C S
authors.initials: CS
authors.lastname: Verbeke
authors.forename: N
authors.initials: N
authors.lastname: Fox
authors.forename: J
authors.initials: J
authors.lastname: Booth
authors.forename: G
authors.initials: G
authors.lastname: Bottley
authors.forename: H S
authors.initials: HS
authors.lastname: Pandha
authors.forename: G E
authors.initials: GE
authors.lastname: Blair
mesh_terms: D000256:Adenoviridae / Q000187:drug effects / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D045744:Cell Line, Tumor; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D005170:Factor X / Q000494:pharmacology*; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D039302:Integrin alphaVbeta3 / Q000378:metabolism; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D034622:RNA Interference; D011991:Receptors, Virus / Q000235:genetics / Q000378:metabolism; D019030:Receptors, Vitronectin / Q000378:metabolism; D014161:Transduction, Genetic
chemical_list: C568771:CLMP protein, human; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D039302:Integrin alphaVbeta3; D011991:Receptors, Virus; D019030:Receptors, Vitronectin; C064660:integrin alphaVbeta5; D005170:Factor X