Department of Surgery, University of Florida College of Medicine, Gainesville, FL, 32610, USA.
Department of Biostatistics, University of Florida College of Medicine, Gainesville, FL, 32610, USA.
Proteomics. 2019 Jul;19(13):e1800394. doi: 10.1002/pmic.201800394. Epub 2019 Jun 11.
Exosomes are membrane-bound vesicles that traffic small molecular cargos. These cargos participate in cell-cell communication and contribute to the pathogenesis of many disease including cancer. How these mechanisms contribute to communication within the pancreatic adenocarcinoma (PDAC) microenvironment and how they contribute to PDAC biology are poorly understood. Performed in this study are comprehensive, quantitative comparisons of the proteomes of three PDAC cell lines to those of the exosomes they produce. Approximately 35% of whole cell proteins sort into exosomes. Analysis of composition of microbiomes (ANCOM) determined a cluster of 98 enriched pancreatic cancer exosome core proteins (ePC-ECPs). Further, these proteins are predicted by ingenuity pathway analysis (IPA) as actively involved in signaling pathways regulating cell death and survival, cellular movement, and cell-to-cell signaling and interaction in particular (top three p-value significant pathways). Significant enrichment of canonical pathways of acute phase response signaling (inflammatory response signaling pathways) and FXR and RXR activation in biosynthetic pathways are also predicted; 97 ePC-ECPs are associated with cancer and among them, 34 are specifically associated with PDAC. In conclusion, exosomes from PDAC are enriched with cancer-associated signaling proteins. Further assessment of these proteins as PDAC biomarkers or therapeutic targets is warranted.
外泌体是一种带有膜的小泡，可运输小分子货物。这些货物参与细胞间通讯，并有助于许多疾病的发病机制，包括癌症。这些机制如何促进胰腺导管腺癌 (PDAC) 微环境中的通讯，以及它们如何促进 PDAC 生物学，目前了解甚少。本研究对三种 PDAC 细胞系的蛋白质组与它们产生的外泌体进行了全面、定量的比较。大约 35%的全细胞蛋白分选到外泌体中。微生物组组成分析 (ANCOM) 确定了一组 98 个富含胰腺癌细胞外泌体核心蛋白 (ePC-ECPs)。此外，通过 ingenuity pathway analysis (IPA) 预测这些蛋白质积极参与调节细胞死亡和存活、细胞运动以及细胞间信号转导和相互作用的信号通路（前三个具有显著意义的通路 p 值）。生物合成途径中还预测到急性期反应信号（炎症反应信号通路）和 FXR 和 RXR 激活的经典途径显著富集；97 个 ePC-ECPs 与癌症相关，其中 34 个与 PDAC 特异性相关。总之，PDAC 的外泌体富含与癌症相关的信号蛋白。进一步评估这些蛋白质作为 PDAC 生物标志物或治疗靶点是有必要的。
