title: Expression of the coxsackie adenovirus receptor in neuroendocrine lung cancers and its implications for oncolytic adenoviral infection.
abstract: Coxsackie adenovirus receptor (CAR) is the primary receptor to which oncolytic adenoviruses have to bind for internalization and viral replication. A total of 171 neuroendocrine lung tumors in form of multitissue arrays have been analyzed resulting in a positivity of 112 cases (65.5%). Immunostaining correlated statistically significant with histopathology and development of recurrence. The subtype small cell lung cancer (SCLC) showed the highest CAR expression (77.6%), moreover the CAR level was correlated to the disease-free survival. Further, high CAR expression level in SCLC cell lines was found in vitro and in vivo when cell lines had been transplanted into immunodeficient mice. A correlation between CAR expression in the primary tumors and metastases development in the tumor model underlined the clinical relevance. Cell lines with high CAR level showed a high infectivity when infected with a replication-deficient adenovirus. Low levels of CAR expression in SCLC could be upregulated with Trichostatin A, a histone deacetylase inhibitor. As a result of the unaltered poor prognosis of SCLC and its high CAR expression it seems to be the perfect candidate for oncolytic therapy. With our clinically relevant tumor model, we show that xenograft experiments are warrant to test the efficiency of oncolytic adenoviral therapy.
authors.affiliation: Department of Anatomy and Experimental Morphology, University Hospital Hamburg-Eppendorf, Hamburg, Germany. t.wunder@uke.de
authors.forename: T
authors.initials: T
authors.lastname: Wunder
authors.forename: K
authors.initials: K
authors.lastname: Schmid
authors.forename: D
authors.initials: D
authors.lastname: Wicklein
authors.forename: P
authors.initials: P
authors.lastname: Groitl
authors.forename: T
authors.initials: T
authors.lastname: Dobner
authors.forename: T
authors.initials: T
authors.lastname: Lange
authors.forename: M
authors.initials: M
authors.lastname: Anders
authors.forename: U
authors.initials: U
authors.lastname: Schumacher
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D045744:Cell Line, Tumor; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein / Q000096:biosynthesis*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000628:therapy; D008297:Male; D051379:Mice; D018358:Neuroendocrine Tumors / Q000378:metabolism* / Q000401:mortality / Q000628:therapy; D050130:Oncolytic Virotherapy; D050504:Oncolytic Viruses / Q000235:genetics; D016016:Proportional Hazards Models; D055752:Small Cell Lung Carcinoma / Q000378:metabolism* / Q000401:mortality / Q000628:therapy; D023041:Xenograft Model Antitumor Assays
chemical_list: D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D006877:Hydroxamic Acids; D049452:Green Fluorescent Proteins; C012589:trichostatin A