Zygalaki Eleni, Tsaroucha Emily G, Kaklamanis Loukas, Lianidou Evi S
Laboratory of Analytical Chemistry, Department of Chemistry, University of Athens, Athens 15771, Greece.
Clin Chem. 2007 Aug;53(8):1433-9. doi: 10.1373/clinchem.2007.086819. Epub 2007 Jun 28.
Vascular endothelial growth factor (VEGF) is a major regulator of angiogenesis and its expression is increased in non-small cell lung cancer (NSCLC). We aimed to determine the expression pattern of VEGF splice variants in NSCLC and its correlation with the clinicopathological characteristics of tumors.
We used real-time reverse transcription PCR to quantify the mRNA expression of total VEGF, 4 VEGF splice variants (VEGF(121), VEGF(165), VEGF(183), and VEGF(189)), and 2 VEGF receptors (VEGFR-1 and VEGFR-2) in 27 pairs of cancerous and adjacent noncancerous tissues originating from patients with NSCLC.
Total VEGF, VEGF(121), and VEGF(165) were expressed in all specimens, whereas VEGF(183) and VEGF(189) were present in small amounts in certain samples. Total VEGF, VEGF(121), and VEGF(165) mRNA was upregulated in cancerous compared with healthy tissues, whereas VEGF(183) and VEGF(189) expression tended to be higher in healthy tissues. The expression of VEGFRs was similar between matched specimens. No correlation was found between the expression of total VEGF or VEGF splice variants and the clinicopathological characteristics of tumors. The expression patterns of VEGF splice variants differed between tissue pairs. VEGF(121) was the major variant expressed in all samples; however, its relative expression was higher in cancerous tissues. The relative expression of VEGF(183) and VEGF(189) was upregulated in healthy lung tissues, whereas the ratio of VEGF(165) to total VEGF was similar between matched specimens.
The expression pattern of certain VEGF splice variants is altered during tumorigenesis. Our data support the hypothesis that during malignant progression an angiogenic switch favoring the shorter diffusible isoforms occurs.
血管内皮生长因子（VEGF）是血管生成的主要调节因子，其在非小细胞肺癌（NSCLC）中表达增加。我们旨在确定VEGF剪接变体在NSCLC中的表达模式及其与肿瘤临床病理特征的相关性。
我们使用实时逆转录PCR定量27对源自NSCLC患者的癌组织和相邻非癌组织中总VEGF、4种VEGF剪接变体（VEGF(121)、VEGF(165)、VEGF(183)和VEGF(189)）以及2种VEGF受体（VEGFR-1和VEGFR-2）的mRNA表达。
所有标本中均表达总VEGF、VEGF(121)和VEGF(165)，而某些样本中少量存在VEGF(183)和VEGF(189)。与健康组织相比，癌组织中总VEGF、VEGF(121)和VEGF(165)的mRNA上调，而VEGF(183)和VEGF(189)在健康组织中的表达往往更高。匹配标本之间VEGFRs的表达相似。未发现总VEGF或VEGF剪接变体的表达与肿瘤的临床病理特征之间存在相关性。组织对之间VEGF剪接变体的表达模式不同。VEGF(121)是所有样本中表达的主要变体；然而，其相对表达在癌组织中更高。VEGF(183)和VEGF(189)在健康肺组织中的相对表达上调，而匹配标本之间VEGF(165)与总VEGF的比率相似。
某些VEGF剪接变体的表达模式在肿瘤发生过程中发生改变。我们的数据支持这样的假设，即在恶性进展过程中发生了有利于较短可扩散异构体的血管生成转换。
