Expression of vascular endothelial growth factor receptors in human prostate cancer
Expression of vascular endothelial growth factor receptors in human prostate cancer
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DOI：
10.1016/s0090-4295(99)00156-9
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发表时间：
1999-09-01
期刊：
影响因子：
2.1
通讯作者：
Kreutzer, DL
中科院分区：
文献类型：
--
作者：
Ferrer, FA;Miller, LJ;Kreutzer, DL
目标.我们最近报道了血管内皮生长因子（VEGF）在人前列腺癌（PCa）中的表达和细胞因子调节。VEGF通过两种高亲和力受体，fms样酪氨酸激酶（FLT-1）和胎肝激酶（FLK-1）发挥其血管生成和促肿瘤发生特性。我们假设这些受体在前列腺癌微环境中表达并控制VEGF功能。在此，我们评估了这些受体在离体前列腺癌组织、良性前列腺肥大（BPH）组织和培养的前列腺癌细胞系中的表达。从接受根治性耻骨后前列腺切除术的患者中获得体外PCa标本。选择包含PCa和BPH组织的标本（n = 15）。使用抗人FLT-1和FLK-1进行免疫组织化学分析，并分析标本以表征两种受体的表达和分布。用免疫细胞化学方法检测前列腺癌细胞系DU-145和LNCaP中FLT-1和FLK-1的表达。在100%的评估标本中，PCa细胞表达VEGF受体FLT-1。FLK-1的表达是可变的，并与肿瘤分级相关;高级别肿瘤显示很少或没有FLK-1表达。PCa区域内的血管内皮细胞（VEC）始终表达FLT-1和FLK-1受体。FLT-1和FLK-1在BPH组织中均有表达。FLT-1在BPH中表达于腺上皮细胞，但在大多数情况下，FLK-1特异性地定位于肥大腺体的基底细胞层。DU-145和LNCaP细胞株表达FLT-1，但不表达FLK-1。尽管FLT-1和FLK-1的表达存在差异，但它们都存在于PCa和BPH中。肿瘤血管内皮细胞上受体的表达支持VEGF在肿瘤微环境中旁分泌刺激内皮细胞中的既定作用。FLT-1和FLK-1在肿瘤细胞上的表达本身表明VEGF具有潜在的自分泌功能（如调节肿瘤细胞增殖）。这些发现意味着VEGF可能存在一种新的双重作用，除了调节内皮细胞功能和随后的新生血管发育的旁分泌作用外，它还参与肿瘤细胞活化（自分泌）。(C)1999年，Elsevier Science Inc.
Objectives. We recently reported the expression and cytokine regulation of vascular endothelial growth factor (VEGF) in human prostate cancer (PCa). VEGF exerts its angiogenic and pro-tumorigenic properties by way of two high affinity receptors, fms-like tyrosine kinase (FLT-1) and fetal liver kinase (FLK-1). We hypothesized that these receptors are expressed and control VEGF functions in the PCa microenvironment. Herein, we evaluate the expression of these receptors in ex vivo PCa tissue, benign prostatic hypertrophy (BPH) tissue, and cultured PCa cell lines.Methods. Ex vivo PCa specimens were obtained from patients undergoing radical retropubic prostatectomy. Specimens were selected to contain both PCa and BPH tissue (n = 15). Immunohistochemical analysis using antihuman FLT-1 and FLK-1 was performed and specimens were analyzed to characterize the expression and distribution of both receptors. Immunocytochemical analysis for FLT-1 and FLK-1 was also performed on cultured PCa cell lines (DU-145 and LNCaP).Results. PCa cells expressed the VEGF receptor FLT-1 in 100% of specimens evaluated. Expression of FLK-1 was variable and related to tumor grade; high-grade tumors displayed little or no FLK-1 expression. Vascular endothelial cells (VECs) within areas of PCa consistently expressed both FLT-1 and FLK-1 receptors. FLT-1 and FLK-1 were both expressed in BPH tissue. FLT-1 was expressed in the glandular epithelial cells in BPH, but in most cases FLK-1 was localized specifically to the basal cell layer of hypertrophic glands. FLT-1, but not FLK-1, was expressed by the DU-145 and LNCaP cell lines.Conclusions. Although they are differentially expressed, both FLT-1 and FLK-1 are present in PCa and BPH. Expression of receptors on VECs of tumor vessels supports the well-established role of VEGF in paracrine stimulation of VECs in the tumor microenvironment. The expression of FLT-1 and FLK-1 on tumor cells themselves suggests a potential autocrine function for VEGF (such as regulating tumor cell proliferation). These findings imply that a novel dual role may exist for VEGF, such that it is involved in tumor cell activation (autocrine), in addition to paracrine actions whereby it regulates endothelial cell functions and subsequent neovascular development. (C) 1999, Elsevier Science Inc.