title: Osteopontin overproduced by tumor cells acts as a potent angiogenic factor contributing to tumor growth.
abstract: Angiogenesis, which is essential for tumor growth, is regulated by various angiogenic factors. Osteopontin (OPN) is expressed in various human tumors and is postulated to be involved in tumor progression. We have recently reported that culture medium with murine neuroblastoma C1300 cells transfected with OPN gene significantly stimulates human umbilical vein endothelial cell migration and induces neovascularization in mice by dorsal air sac assay. However, the effect of OPN on tumorigenesis as an angiogenic factor remains to be clarified. In this study, we injected the OPN-transfected C1300 cells and control cells into the nude mice subcutaneously. OPN-overexpressing C1300 cells significantly formed rapidly growing tumor as compared to the control cells in mice, although in vitro and in vivo cell growth rates were similar. In vivo tumorigenecity of these cells correlated with the amount of secreted OPN protein. In addition, neovascularization of OPN-transfected tumor was significantly increased in comparison with those of control cells by immunohistochemistry for CD31. In vitro chemoinvasiveness and gene expression of proteases including uPA, MMP2, 9, MT1-MMP, and cathepsin B, D, L, were not different between OPN-transfected and control cells determined with matrigel invasion assay and cDNA expression macroarray, respectively. Conclusively, these results strongly imply that OPN plays an important role in tumor growth through the enhancement of angiogenesis in vivo.
authors.affiliation: Department of Respiratory Medicine, Juntendo University, School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan.
authors.forename: Michihiro
authors.initials: M
authors.lastname: Hirama
authors.forename: Fumiyuki
authors.initials: F
authors.lastname: Takahashi
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Takahashi
authors.forename: Shigeru
authors.initials: S
authors.lastname: Akutagawa
authors.forename: Kazue
authors.initials: K
authors.lastname: Shimizu
authors.forename: Sanae
authors.initials: S
authors.lastname: Soma
authors.forename: Yuri
authors.initials: Y
authors.lastname: Shimanuki
authors.forename: Kazuto
authors.initials: K
authors.lastname: Nishio
authors.forename: Yoshinosuke
authors.initials: Y
authors.lastname: Fukuchi
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis; D002455:Cell Division; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009447:Neuroblastoma / Q000235:genetics*; D053495:Osteopontin; D012795:Sialoglycoproteins / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology*; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D043925:Angiogenesis Inducing Agents; C506895:SPP1 protein, human; D012795:Sialoglycoproteins; C506896:Spp1 protein, mouse; D053495:Osteopontin