Antiangiogenic activity of BAI1 in vivo: implications for gene therapy of human glioblastomas

• Published in: Cancer gene therapy Vol. 13; no. 4; pp. 385 - 392
• Main Authors: Kang, X, Xiao, X, Harata, M, Bai, Y, Nakazaki, Y, Soda, Y, Kurita, R, Tanaka, T, Komine, F, Izawa, K, Kunisaki, R, Setoyama, M, Nishimori, H, Natsume, A, Sunamura, M, Lozonshi, L, Saitoh, I, Tokino, T, Asano, S, Nakamura, Y, Tani, K
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01-04-2006
• Subjects: Adenoviridae - genetics; Angiogenesis; Angiogenesis inhibitors; Angiogenic Proteins - biosynthesis; Angiogenic Proteins - genetics; Animals; Antitumor activity; Astrocytoma; Brain cancer; Brain Neoplasms - blood supply; Brain Neoplasms - pathology; Brain Neoplasms - therapy; Brain tumors; Care and treatment; Cell Line, Tumor; Dosage and administration; Gene expression; Gene therapy; Genetic aspects; Genetic Therapy; Genetic Vectors; Glioblastoma; Glioblastoma - blood supply; Glioblastoma - pathology; Glioblastoma - therapy; Glioblastoma cells; Glioblastoma multiforme; Health aspects; Humans; Inoculation; Methods; Mice; Mice, SCID; mRNA; Neoplasm Transplantation; Neovascularization, Pathologic - therapy; RNA, Messenger - metabolism; Transduction, Genetic; Tumor cells; Tumors; Vascular endothelial growth factor; Vascularization; Japan
• ISSN: 0929-1903; 1476-5500
• DOI: 10.1038/sj.cgt.7700898

Glioblastomas are the most common primary brain tumors in adults. These tumors exhibit a high degree of vascularization, and malignant progression from astrocytoma to glioblastoma is often accompanied by increased angiogenesis and the upregulation of vascular endothelial growth factor and its receptors. In this study, we investigated the in vivo antiangiogenic and antitumor effects of brain-specific angiogenesis inhibitor 1 (BAI1) using human glioblastoma cell lines. Glioblastoma cells were transduced with an adenoviral vector encoding BAI1 (AdBAI1), and Northern and Western blot analyses, respectively, demonstrated BAI1 mRNA and protein expression in the transduced tumor cells. Using an in vivo neovascularization assay, we found that angiogenesis surrounding AdBAI1-transduced glioblastoma cells transplanted into transparent skinfold chambers of SCID mice was significantly impaired compared to control treated cells. Additionally, in vivo inoculation with AdBAI1 of established subcutaneous or intracerebral transplanted tumors significantly impaired tumor growth and promoted increased mouse survival. Morphologically, the tumors exhibited signs of impaired angiogenesis, such as extensive necrosis and reduced intratumoral vascular density. Taken together, these data strongly indicate that BAI1 may be an excellent gene therapy candidate for the treatment of brain tumors, especially human glioblastomas.