title: Cell-retained isoforms of vascular endothelial growth factor (VEGF) are correlated with poor prognosis in osteosarcoma.
abstract: Vascular endothelial growth factor (VEGF) is a major angiogenic factor. Osteosarcoma is characterised by hypervascularity and metastatic potential. We examined VEGF mRNA expression, VEGF isoform pattern and VEGF receptor (flt-1 and KDR) by RT-PCR analysis in 30 osteosarcomas. All 30 osteosarcomas expressed VEGF mRNA. 17 osteosarcomas (57%) expressed flt-1 mRNA, whilst 20 (67%) expressed KDR mRNA. 6/30 (20%) osteosarcomas were positive for VEGF121 only, 8 (27%) for VEGF121 + VEGF165, and 16 (53%) for VEGF121 + VEGF165 + VEGF189. Patients with osteosarcomas with VEGF165 (n = 24) had significantly poorer prognosis in comparison with those without VEGF165 (P = 0.022, Wilcoxon's test). The osteosarcomas with VEGF165 had significantly increased vascularity assessed on sections immunostained for CD34 (P < 0.001, Mann-Whitney U test). Although VEGF165 is a soluble isoform, it is also retained on the cellular surface. These results suggest that cell-retained VEGF isoforms (VEGF165, VEGF189) might be essential for neovascularisation in osteosarcoma, whilst the soluble VEGF121 isoform is not sufficient to stimulate neovascularisation in this type of neoplasm.
authors.affiliation: Department of Pathology, Tokai University School of Medicine, Kanagawa, Japan.
authors.forename: Y H
authors.initials: YH
authors.lastname: Lee
authors.forename: T
authors.initials: T
authors.lastname: Tokunaga
authors.forename: Y
authors.initials: Y
authors.lastname: Oshika
authors.forename: R
authors.initials: R
authors.lastname: Suto
authors.forename: K
authors.initials: K
authors.lastname: Yanagisawa
authors.forename: M
authors.initials: M
authors.lastname: Tomisawa
authors.forename: H
authors.initials: H
authors.lastname: Fukuda
authors.forename: H
authors.initials: H
authors.lastname: Nakano
authors.forename: S
authors.initials: S
authors.lastname: Abe
authors.forename: A
authors.initials: A
authors.lastname: Tateishi
authors.forename: H
authors.initials: H
authors.lastname: Kijima
authors.forename: H
authors.initials: H
authors.lastname: Yamazaki
authors.forename: N
authors.initials: N
authors.lastname: Tamaoki
authors.forename: Y
authors.initials: Y
authors.lastname: Ueyama
authors.forename: M
authors.initials: M
authors.lastname: Nakamura
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001859:Bone Neoplasms / Q000378:metabolism*; D016228:Endothelial Growth Factors / Q000378:metabolism*; D005260:Female; D006801:Humans; D008222:Lymphokines / Q000378:metabolism*; D008297:Male; D051379:Mice; D016513:Mice, SCID; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic; D012516:Osteosarcoma / Q000098:blood supply / Q000378:metabolism*; D011379:Prognosis; D020033:Protein Isoforms / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D014183:Transplantation, Heterologous; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
chemical_list: D016228:Endothelial Growth Factors; D008222:Lymphokines; D009363:Neoplasm Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors