Expression of the coxsackie and adenovirus receptor in human astrocytic tumors and xenografts.
The sensitivity of human tissues and tumors to infection with type C adenoviruses correlates with the expression of the human coxsackie B- and adenovirus receptor, hCAR. HCAR is heterogeneously expressed in various tissues and types of human cancer cells, which has implications for the use of adenoviruses as vectors in cancer gene therapy. Using immunoblotting, real-time PCR, FACS-analysis and sensitivity to infection with adenovirus-lacZ, we analyzed the expression level of hCAR in glioma Grade IV cell lines. With real-time PCR, we also analyzed hCAR expression in primary human astrocytomas of different malignancy grades, as well as in their xenograft derivatives. Analysis of a set of 10 cell lines showed great variation in hCAR expression. Susceptibility to Ad5lacZ correlated well with hCAR expression, whereas no correlation was observed with the expression of alphavbeta3/alphavbeta5 integrins, proposed to function as co-receptors for adenoviruses. A great variation of CAR expression was also observed in primary astrocytomas of different malignancy grades. The mean value of CAR expression was significantly lower in 22 Grade IV tumors as compared to the values for 6 Grade II (p = 0.01) and 6 Grade III (p = 0.01) tumors. When the hCAR expression in 11 xenografts derived from Grade IV gliomas were compared to the levels detected in the original parental tumors, a mean 12-fold higher expression was seen in the xenografts (P = 0.01). Two xenografts with low hCAR expression grew considerably faster than the hCAR-expressing cells. Our results have relevance for the use of adenoviruses in gene therapy against astrocytomas.
Fuxe
Jonas
J
Ludwig Institute for Cancer Research, Stockholm Branch, Stockholm, Sweden.
Liu
Lu
L
Malin
Stephen
S
Philipson
Lennart
L
Collins
V Peter
VP
Pettersson
Ralf F
RF
D000256:Adenoviridae / Q000502:physiology; D000818:Animals; D001254:Astrocytoma / Q000378:metabolism* / Q000821:virology; D001932:Brain Neoplasms / Q000378:metabolism* / Q000821:virology; D037281:Calnexin / Q000378:metabolism; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D004770:Enterovirus / Q000502:physiology; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D015316:Genetic Therapy; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000378:metabolism; D016023:Integrins / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000378:metabolism / Q000628:therapy; D012333:RNA, Messenger / Q000378:metabolism; D011991:Receptors, Virus / Q000235:genetics / Q000378:metabolism*; D019030:Receptors, Vitronectin / Q000378:metabolism; D012867:Skin / Q000378:metabolism; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D001616:beta-Galactosidase / Q000235:genetics / Q000378:metabolism
C568771:CLMP protein, human; C568772:CLMP protein, mouse; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D039302:Integrin alphaVbeta3; D016023:Integrins; D012333:RNA, Messenger; D011991:Receptors, Virus; D019030:Receptors, Vitronectin; C064660:integrin alphaVbeta5; D037281:Calnexin; D001616:beta-Galactosidase