Variable expression of coxsackie-adenovirus receptor in thyroid tumors: implications for adenoviral gene therapy.
Adenoviral gene therapy represents a novel approach for the treatment of aggressive thyroid carcinomas. Both coxsackie-adenovirus receptor (CAR) and integrins have been shown to be the major determinants for adenoviral infectivity in many types of cancer cells, yet conflicting results have been reported. In this report we examine these factors mediating adenoviral infection in thyroid cells and to evaluate CAR expression in various types of thyroid cancer. We found that neither expression levels of CAR nor integrins are solely predictive of adenoviral infectivity in thyroid cells. However, the absence of CAR was associated with poor adenoviral infectivity in immortalized rat FRTL-5 cells. Moreover, preincubation with alpha-CAR antibody decreased infectivity in FTC 238 cells, a human thyroid tumor line. These results indicate that CAR does play a role in adenoviral infection of thyroid cells. Immunohistochemical analysis revealed that CAR is expressed at the cell surface in the majority of malignant thyroid tumors. We further show that adenoviral infectivity in some thyroid cancer cells can be improved by poly-L-lysine. Our study warrants a functional method to evaluate adenoviral infectivity should be developed and instituted prior to clinical trials of adenoviral gene therapy in patients with advanced thyroid cancer.
Marsee
Derek K
DK
Medical Scientist Program, The Ohio State University, Columbus, Ohio, USA.
Vadysirisack
Douangsone D
DD
Morrison
Carl D
CD
Prasad
Manju L
ML
Eng
Charis
C
Duh
Quan-Yang
QY
Rauen
Katherine A
KA
Kloos
Richard T
RT
Jhiang
Sissy M
SM
D000256:Adenoviridae / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D045744:Cell Line, Tumor; D004770:Enterovirus / Q000235:genetics* / Q000378:metabolism*; D005434:Flow Cytometry; D015316:Genetic Therapy; D007150:Immunohistochemistry; D039302:Integrin alphaVbeta3 / Q000235:genetics; D016023:Integrins / Q000235:genetics; D010957:Plasmids / Q000235:genetics; D011107:Polylysine / Q000378:metabolism; D051381:Rats; D011991:Receptors, Virus / Q000187:drug effects* / Q000235:genetics; D019030:Receptors, Vitronectin / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013964:Thyroid Neoplasms / Q000235:genetics / Q000628:therapy* / Q000821:virology*
D039302:Integrin alphaVbeta3; D016023:Integrins; D011991:Receptors, Virus; D019030:Receptors, Vitronectin; C064660:integrin alphaVbeta5; D011107:Polylysine