Adenovirus-mediated endostatin delivery results in inhibition of mammary gland tumor growth in C3(1)/SV40 T-antigen transgenic mice.
We demonstrate the efficacy of systemic administration of a replication-defective adenovirus expressing endostatin (Ad-mEndo) administered during the preinvasive stage of mammary tumor development in C3(1)/T antigen transgenic mice. Mean serum levels of endostatin increased about 8-fold above that of controls and resulted in a significant decrease in tumor growth and an increase in survival. The inhibitory effect of endostatin occurred during or after the progression to invasive carcinoma. Reduced levels of vascular endothelial growth factor mRNA were found in association with high levels of endostatin. Our results demonstrate that the adenoviral induction of high levels of circulating endostatin significantly inhibits mammary tumor growth during the period when the "angiogenic switch" occurs.
Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA.
Alfonso
A
Calvo
Andrew L
AL
Feldman
Steven K
SK
Libutti
Jeffrey E
JE
Green
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000235:genetics; D002455:Cell Division / Q000502:physiology; D003094:Collagen / Q000096:biosynthesis / Q000097:blood / Q000235:genetics*; D043169:Endostatins; D016228:Endothelial Growth Factors / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D008222:Lymphokines / Q000096:biosynthesis / Q000235:genetics; D008325:Mammary Neoplasms, Experimental / Q000097:blood / Q000098:blood supply* / Q000235:genetics / Q000628:therapy*; D051379:Mice; D008812:Mice, Hairless; D008822:Mice, Transgenic; D009389:Neovascularization, Pathologic / Q000097:blood / Q000628:therapy*; D010446:Peptide Fragments / Q000096:biosynthesis / Q000097:blood / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D000952:Antigens, Polyomavirus Transforming; D043169:Endostatins; D016228:Endothelial Growth Factors; D008222:Lymphokines; D010446:Peptide Fragments; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D003094:Collagen