title: Control of angiogenesis by VEGF and endostatin-encapsulated protein microcrystals and inhibition of tumor angiogenesis.
abstract: Encapsulation of cytokines within protein microcrystals (polyhedra) is a promising approach for the stabilization and delivery of therapeutic proteins. Here, we investigate the influence of vascular endothelial growth factor (VEGF) microcrystals and endostatin microcrystals on angiogenesis. VEGF was successfully encapsulated into microcrystals derived from insect cypovirus with overexpression of protein disulfide bond isomerase. VEGF microcrystals were observed to increase the phosphorylation of p42/p44 MAP kinase and to stimulate the proliferation, migration, and network and tube formation of human umbilical vein endothelial cells (HUVECs). Endostatin was also successfully encapsulated into microcrystals. Endostatin microcrystals showed antiangiogenesis activities and inhibited the migration, and network and tube formation of HUVECs. Local administration of endostatin microcrystals in mice inhibited both angiogenesis and tumor growth with clear significant differences between treatment and control groups. Endostatin microcrystals only affected angiogenesis, but had no significant effect on lymphangiogenesis compared to controls. Local therapy using endostatin microcrystals offers a potential approach to achieve sustained therapeutic release of antiangiogenic molecules for cancer treatment.
authors.affiliation: Division of Oral Surgery, Yokohama Clinical Education Center of Kanagawa Dental University, 3-31-6 Tsuruya-cho, Kanagawa-ku, Yokohama 221-0835, Japan.
authors.forename: Goichi
authors.initials: G
authors.lastname: Matsumoto
authors.forename: Rie
authors.initials: R
authors.lastname: Hirohata
authors.forename: Kousuke
authors.initials: K
authors.lastname: Hayashi
authors.forename: Yoko
authors.initials: Y
authors.lastname: Sugimoto
authors.forename: Eiji
authors.initials: E
authors.lastname: Kotani
authors.forename: Junji
authors.initials: J
authors.lastname: Shimabukuro
authors.forename: Tomoko
authors.initials: T
authors.lastname: Hirano
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Nakajima
authors.forename: Shin
authors.initials: S
authors.lastname: Kawamata
authors.forename: Hajime
authors.initials: H
authors.lastname: Mori
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003460:Crystallization; D004337:Drug Carriers / Q000737:chemistry; D043169:Endostatins / Q000008:administration & dosage* / Q000494:pharmacology; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000098:blood supply / Q000188:drug therapy; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage* / Q000494:pharmacology
chemical_list: D004337:Drug Carriers; D043169:Endostatins; D042461:Vascular Endothelial Growth Factor A
keywords: Angiogenesis; Antiangiogenesis; Endostatin; Polyhedra; VEGF