Exosomal miR-205-5p inhibits lymphatic metastasis in pancreatic cancer through diffusely downregulating VEGFA

Pancreatic ductal adenocarcinoma (PDAC) is to become the second leading cause of cancer-related deaths by 2040. This study aimed to identify potential miRNA landmarks for lymph node metastasis and to elucidate the underlying mechanisms in PDAC. Materials and Methods: A total of 14 peripheral blood samples were collected from patients with PDAC (7 at N0 stage and 7 at N2 stage) following appropriate inclusion and exclusion criteria. The plasma exosomes were extracted with Size Exclusion Chromatography (SEC). Tissue Microarray (TMA) and in situ hybridization (ISH) assay were used to detect miR-205-5p expression in human tissues. Cell-derived exosomes were collected by ultra high-speed centrifugation. PKH-67 staining was used to illustrate the uptake of exosomes by cells. GW4869 was used to block the secretion of exosomes. Subcutaneous tumor model and lymph node metastasis model were applied to monitor proliferation and lymph node metastasis in vivo, respectively.

至2040年，胰腺导管腺癌（PDAC）将成为癌症相关死亡的第二大诱因。本研究旨在筛选可用于胰腺导管腺癌淋巴结转移的潜在微小RNA（miRNA）标志物，并阐明其潜在分子机制。材料与方法：本研究严格遵循纳入与排除标准，共采集14例胰腺导管腺癌患者的外周血样本，其中N0期、N2期患者各7例。采用尺寸排阻色谱法（Size Exclusion Chromatography, SEC）提取血浆外泌体。通过组织微阵列（Tissue Microarray, TMA）与原位杂交（in situ hybridization, ISH）技术检测人组织中miR-205-5p的表达水平。采用超速离心法分离获取细胞源性外泌体。使用PKH-67染色法示踪细胞对外泌体的摄取过程。利用GW4869阻断外泌体的分泌。分别构建皮下移植瘤模型与淋巴结转移模型，以在体监测肿瘤增殖与淋巴结转移情况。