Hayes A J, Huang W Q, Yu J, Maisonpierre P C, Liu A, Kern F G, Lippman M E, McLeskey S W, Li L Y
Department of Oncology, Department of Biostatistics, Georgetown University Medical Center, 3970 Reservoir Road, NW RB/E301, Washington, DC 20007, USA.
Br J Cancer. 2000 Nov;83(9):1154-60. doi: 10.1054/bjoc.2000.1437.
Angiopoietin-1 (Ang1) has been shown to act as an angiogenic promoter in embryonic angiogenesis by promoting vascular branching, pericyte recruitment and endothelial survival. We have investigated the role of Ang1 in tumour neovascularization under clinical conditions and in animal models. The expression of Ang1 in clinical breast cancer specimens was analysed by using laser-capture microdissection and reverse transcriptase-linked polymerase chain reaction (RT-PCR) on RNA isolated from the samples. Despite the expression of Ang1 in many human breast cancer cell lines, the gene was expressed in only three of 21 breast cancer clinical specimens, even though its receptor, Tie2, is abundant in the vasculature of all of these tumours. Ang1 was then overexpressed in a human breast cancer cell line (MCF-7) on its own and in conjunction with FGF1, an angiogenic factor shown to be able to increase the tumorigenicity of MCF-7 cells. High concentrations of Ang1 were produced in the conditioned media of the transfected cells (range 156-820 ng ml(-1)). However, in contrast to its physiological role as promoter of angiogenesis, overexpression of Ang1 did not enhance tumour growth, but instead caused up to a 3-fold retardation of tumour growth (P = 0.003).
血管生成素-1（Ang1）已被证明在胚胎血管生成中作为血管生成促进因子，通过促进血管分支、周细胞募集和内皮细胞存活发挥作用。我们研究了Ang1在临床条件下和动物模型中肿瘤新生血管形成中的作用。通过激光捕获显微切割技术，并对从样本中分离的RNA进行逆转录聚合酶链反应（RT-PCR），分析了临床乳腺癌标本中Ang1的表达情况。尽管在许多人乳腺癌细胞系中存在Ang1的表达，但在21份乳腺癌临床标本中只有3份标本的该基因表达，即便其受体Tie2在所有这些肿瘤的脉管系统中都大量存在。然后，在人乳腺癌细胞系（MCF-7）中单独或与血管生成因子FGF1共同过表达Ang1，FGF1已被证明能够增加MCF-7细胞的致瘤性。在转染细胞的条件培养基中产生了高浓度的Ang1（范围为156 - 820 ng ml(-1)）。然而，与它作为血管生成促进因子的生理作用相反，Ang1的过表达并未促进肿瘤生长，反而导致肿瘤生长延缓达3倍（P = 0.003）。
