Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA; Walther Oncology Center, Indianapolis, IN, USA; Indiana University Simon Cancer Center, Indianapolis, IN, USA; Indiana University Health Pancreatic Cyst and Cancer Early Detection Center, Indianapolis, IN, USA.
Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA; Indiana University Health Pancreatic Cyst and Cancer Early Detection Center, Indianapolis, IN, USA.
Biochimie. 2021 Feb;181:234-239. doi: 10.1016/j.biochi.2020.12.016. Epub 2020 Dec 30.
Vascular endothelial growth factor (VEGF)-A is known to play key biological roles in angiogenesis and vascular permeability. We previously identified VEGF-A as an accurate biomarker of benign pancreatic cystic lesions known as serous cystic neoplasms (SCN). In the present study, we seek to further characterize the expression of VEGF-A and its splice isoforms in different pancreatic cysts including SCN. Patients undergoing surgery were consented for the collection of pancreatic cystic lesion tissue (SCN, pseudocysts, mucinous cysts) and normal adjacent pancreas as well as pancreatic cyst fluid. Following RNA isolation from the tissues, relative VEGF-A gene expression was quantitatively analyzed using real-time PCR (qPCR), and VEGF-A isoform expression was evaluated by reverse transcriptase (RT)-PCR. Relative VEGF-A gene expression was significantly increased in SCN, demonstrating transcriptional upregulation in SCN compared to other pancreatic cyst tissues (P < 0.0001). VEGF-189, -165, -145, and -121 splice variants were detected in both normal adjacent pancreas and pancreatic cystic lesions; the novel VEGF-111 isoform was variably expressed in normal and cyst tissues. Finally, VEGF isoform levels in pancreatic cyst fluid were measured by isoform-specific ELISAs. VEGF-165, -145, and -121 proteins were present in pancreatic cyst fluids; VEGF-165 levels were significantly higher in SCN cyst fluid. Thus, multiple VEGF isoforms were expressed in normal pancreas and pancreatic cysts. Of particular interest are VEGF-145 and -111, which have not previously been described in human pancreas where they may exhibit unique biological activities in health and/or disease.
血管内皮生长因子（VEGF）-A 已知在血管生成和血管通透性中发挥关键的生物学作用。我们之前已经确定 VEGF-A 是一种准确的生物标志物，可用于识别称为浆液性囊腺瘤（SCN）的良性胰腺囊性病变。在本研究中，我们试图进一步描述不同胰腺囊肿中 VEGF-A 及其剪接异构体的表达情况，包括 SCN。接受手术的患者同意收集胰腺囊性病变组织（SCN、假性囊肿、黏液性囊肿）和正常相邻胰腺以及胰腺囊液。从组织中分离出 RNA 后，使用实时 PCR（qPCR）定量分析相对 VEGF-A 基因表达，并通过逆转录（RT）-PCR 评估 VEGF-A 异构体的表达。SCN 中的相对 VEGF-A 基因表达显著增加，表明与其他胰腺囊性组织相比，SCN 中的转录上调（P < 0.0001）。在正常相邻胰腺和胰腺囊性病变中均检测到 VEGF-189、-165、-145 和 -121 剪接变体；新型 VEGF-111 异构体在正常和囊肿组织中差异表达。最后，通过同工型特异性 ELISA 测量胰腺囊液中的 VEGF 同工型水平。VEGF-165、-145 和 -121 蛋白存在于胰腺囊液中；SCN 囊液中的 VEGF-165 水平显著升高。因此，多种 VEGF 同工型在正常胰腺和胰腺囊肿中表达。特别值得关注的是 VEGF-145 和 -111，它们以前在人类胰腺中尚未被描述过，在健康和/或疾病中可能具有独特的生物学活性。
