title: Osteosarcoma cells enhance angiogenesis visualized by color-coded imaging in the in vivo Gelfoam® assay.
abstract: We previously described a color-coded imaging model that can quantify the length of nascent blood vessels using Gelfoam® implanted in nestin-driven green fluorescent protein (ND-GFP) nude mice. In ND-GFP mice, nascent blood vessels are labeled with GFP. We report here that osteosarcoma cells promote angiogenesis in the Gelfoam® angiogenesis assay in ND-GFP mice. Gelfoam® was initially transplanted subcutaneously in the flank of transgenic ND-GFP nude mice. Seven days after transplantation of Gelfoam®, skin flaps were made and human 143B osteosarcoma cells expressing green fluorescent protein (GFP) in the nucleus and red fluorescent protein (RFP) in cytoplasm were injected into the transplanted Gelfoam®. The control-group mice had only implanted Gelfoam®. Skin flaps were made at days 14, 21, and 28 after transplantation of the Gelfoam® to allow imaging of vascularization in the Gelfoam® using a variable-magnification small animal imaging system and confocal fluorescence microscopy. ND-GFP expressing nascent blood vessels penetrated and spread into the Gelfoam® in a time-dependent manner in both control and osteosarcoma-implanted mice. ND-GFP expressing blood vessels in the Gelfoam® of the osteosarcoma-implanted mice were associated with the cancer cells and larger and longer than in the Gelfoam®-only implanted mice (P < 0.01). The results presented in this report demonstrate strong angiogenesis induction by osteosarcoma cells and suggest this process is a potential therapeutic target for this disease.
authors.affiliation: AntiCancer, Inc., 7917 Ostrow Street, San Diego, California, 92111; Department of Surgery, University of California, 200 West Arbor Drive, San Diego, California, 92103; Department of Orthopedic Surgery, Graduate School of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Okinawa, 903-0125, Japan.
authors.forename: Fuminari
authors.initials: F
authors.lastname: Uehara
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Tome
authors.forename: Shinji
authors.initials: S
authors.lastname: Miwa
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Hiroshima
authors.forename: Shuya
authors.initials: S
authors.lastname: Yano
authors.forename: Mako
authors.initials: M
authors.lastname: Yamamoto
authors.forename: Sumiyuki
authors.initials: S
authors.lastname: Mii
authors.forename: Hiroki
authors.initials: H
authors.lastname: Maehara
authors.forename: Michael
authors.initials: M
authors.lastname: Bouvet
authors.forename: Fuminori
authors.initials: F
authors.lastname: Kanaya
authors.forename: Robert M
authors.initials: RM
authors.lastname: Hoffman
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D005781:Gelatin Sponge, Absorbable; D049452:Green Fluorescent Proteins / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D020007:Implants, Experimental; D008164:Luminescent Proteins / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D008819:Mice, Nude; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D012516:Osteosarcoma / Q000098:blood supply*; D000097573:Red Fluorescent Protein
chemical_list: D049452:Green Fluorescent Proteins; D008164:Luminescent Proteins; D000097573:Red Fluorescent Protein
keywords: ANGIOGENESIS; CONFOCAL MICROSCOPY; GELFOAM®; GREEN FLUORESCENT PROTEIN; NESTIN; OSTEOSARCOMA; RED FLUORESCENT PROTEIN; TRANSGENIC NUDE MOUSE