Expression of the coxsackie adenovirus receptor in neuroendocrine lung cancers and its implications for oncolytic adenoviral infection.
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Expression of the coxsackie adenovirus receptor in neuroendocrine lung cancers and its implications for oncolytic adenoviral infection. / Wunder, Tina; Schmid, Katharina; Wicklein, Daniel; Groitl, P; Dobner, T; Lange, Tobias; Anders, Mario; Schumacher, Udo.
in: CANCER GENE THER, Jahrgang 20, Nr. 1, 1, 2013, S. 25-32.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Expression of the coxsackie adenovirus receptor in neuroendocrine lung cancers and its implications for oncolytic adenoviral infection.
AU - Wunder, Tina
AU - Schmid, Katharina
AU - Wicklein, Daniel
AU - Groitl, P
AU - Dobner, T
AU - Lange, Tobias
AU - Anders, Mario
AU - Schumacher, Udo
PY - 2013
Y1 - 2013
N2 - 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.
AB - 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.
KW - Animals
KW - Humans
KW - Male
KW - Female
KW - Proportional Hazards Models
KW - Mice
KW - Cell Line, Tumor
KW - Kaplan-Meier Estimate
KW - Xenograft Model Antitumor Assays
KW - Adenoviridae/genetics
KW - Gene Expression/drug effects
KW - Coxsackie and Adenovirus Receptor-Like Membrane Protein/biosynthesis
KW - Green Fluorescent Proteins/biosynthesis/genetics
KW - Hydroxamic Acids/pharmacology
KW - Lung Neoplasms/metabolism/mortality/therapy
KW - Neuroendocrine Tumors/metabolism/mortality/therapy
KW - Oncolytic Virotherapy
KW - Oncolytic Viruses/genetics
KW - Small Cell Lung Carcinoma/metabolism/mortality/therapy
KW - Animals
KW - Humans
KW - Male
KW - Female
KW - Proportional Hazards Models
KW - Mice
KW - Cell Line, Tumor
KW - Kaplan-Meier Estimate
KW - Xenograft Model Antitumor Assays
KW - Adenoviridae/genetics
KW - Gene Expression/drug effects
KW - Coxsackie and Adenovirus Receptor-Like Membrane Protein/biosynthesis
KW - Green Fluorescent Proteins/biosynthesis/genetics
KW - Hydroxamic Acids/pharmacology
KW - Lung Neoplasms/metabolism/mortality/therapy
KW - Neuroendocrine Tumors/metabolism/mortality/therapy
KW - Oncolytic Virotherapy
KW - Oncolytic Viruses/genetics
KW - Small Cell Lung Carcinoma/metabolism/mortality/therapy
M3 - SCORING: Journal article
VL - 20
SP - 25
EP - 32
JO - CANCER GENE THER
JF - CANCER GENE THER
SN - 0929-1903
IS - 1
M1 - 1
ER -
