Cell-retained isoforms of vascular endothelial growth factor (VEGF) are correlated with poor prognosis in osteosarcoma

Cell-retained isoforms of vascular endothelial growth factor (VEGF) are correlated with poor prognosis in osteosarcoma
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DOI:
10.1016/s0959-8049(99)00073-8
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发表时间:
1999-07-01
影响因子:
8.4
通讯作者:
Nakamura, M
Nakamura, M
中科院分区:
医学1区
文献类型:
--
作者:
Lee, YH;Tokunaga, T;Nakamura, M

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血管内皮生长因子(VEGF)是一种主要的血管生成因子。骨肉瘤的特点是血管丰富和转移潜力。我们用RT-PCR方法检测了30例骨肉瘤中VEGFmRNA表达、VEGF亚型和VEGF受体(flt-1和KDR)。30例骨肉瘤均表达VEGFmRNA。17例(57%)骨肉瘤表达fit-1 mRNA,20例(67%)表达KDR mRNA。6/30例(20%)骨肉瘤仅VEGF 121阳性,8例(27%)VEGF 121 + VEGF 165阳性,16例(53%)VEGF 121 + VEGF 165 + VEGF 189阳性。与无VEGF 165的患者相比,VEGF 165的骨肉瘤患者(n = 24)的预后明显较差(P = 0.022,Wilcoxon检验)。在CD 34免疫染色的切片上,VEGF 165的骨肉瘤具有显著增加的血管分布(P < 0.001,Mann-Whitney U检验)。尽管VEGF 165是一种可溶性亚型,但它也保留在细胞表面。这些结果表明,细胞保留的VEGF异构体(VEGF 165,VEGF 189)可能是必不可少的新血管形成的骨肉瘤,而可溶性VEGF 121异构体是不足以刺激这种类型的肿瘤的新血管形成。(C)1999 Elsevier Science Ltd.保留所有权利。
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 fit-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. (C) 1999 Elsevier Science Ltd. All rights reserved.