Application of a tumor suppressor (C-CAM1)-expressing recombinant adenovirus in androgen-independent human prostate cancer therapy: a preclinical study.
Recently, we demonstrated that an androgen-regulated cell adhesion molecule, C-CAM, acts as a tumor suppressor in prostate cancer development. In this study, we further explored the possibility of applying C-CAM as a potential agent for developing prostate cancer gene therapy using an adenoviral delivery system. We found that prostate cancer cells, in general, were sensitive to adenoviral infection. In vitro characterization indicated that C-CAM1 protein was detected only in C-CAM1 adenovirus-infected cells but not in antisense control virus-infected cells, and the levels of expression showed dose dependency. Because of the stability of the protein, C-CAM expression in viral-infected cells appeared to be a long-lasting event, indicating that C-CAM may be superior to many other known tumor suppressors that have a short protein half-life. Most importantly, the delivery of a single dose of C-CAM adenovirus was able to repress the growth of PC-3-induced tumors in nude mice for at least 3 weeks. Taken together, these data indicate that C-CAM is a potential candidate for human prostate cancer therapy.
Kleinerman
D I
DI
Department of Urology, University of Texas M. D., Anderson Cancer Center, Houston 77030, USA.
Zhang
W W
WW
Lin
S H
SH
Nguyen
T V
TV
von Eschenbach
A C
AC
Hsieh
J T
JT
D000251:Adenosine Triphosphatases / Q000008:administration & dosage*; D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D015703:Antigens, CD; D001483:Base Sequence; D002272:Carcinoembryonic Antigen; D015815:Cell Adhesion Molecules / Q000008:administration & dosage*; D017931:DNA Primers / Q000737:chemistry; D018014:Gene Transfer Techniques; D016147:Genes, Tumor Suppressor; D015316:Genetic Therapy; D006023:Glycoproteins; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D009368:Neoplasm Transplantation; D011471:Prostatic Neoplasms / Q000628:therapy*; D011994:Recombinant Proteins; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; C069847:CD66 antigens; D002272:Carcinoembryonic Antigen; C486183:Ceacam1 protein, mouse; C087701:Ceacam2 protein, mouse; D015815:Cell Adhesion Molecules; D017931:DNA Primers; D006023:Glycoproteins; D011994:Recombinant Proteins; D000251:Adenosine Triphosphatases