Oncogenic and Non-Malignant Pancreatic Exosome Cargo Reveal Distinct Expression of Oncogenic and Prognostic Factors Involved in Tumor Invasion and Metastasis
Oncogenic and Non-Malignant Pancreatic Exosome Cargo Reveal Distinct Expression of Oncogenic and Prognostic Factors Involved in Tumor Invasion and Metastasis
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DOI：
10.1002/pmic.201800158
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发表时间：
2019-04-01
期刊：
影响因子：
3.4
通讯作者：
Falasca, Marco
中科院分区：
文献类型：
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作者：
Emmanouilidi, Aikaterini;Paladin, Dino;Falasca, Marco
外泌体是细胞外膜小泡，在细胞间通讯中起重要作用，其致癌货物归因于肿瘤进展和转移前生态位的形成。为了深入了解外泌体致癌成分的关键差异，我们利用了人类非恶性上皮和胰腺癌细胞模型以及纯化和表征的外泌体群体。蛋白质组学分析显示，与亲代细胞相比，已知的外泌体标记物和信号蛋白选择性富集。重要的是，提供了对胰腺癌进展的关键转移调节因子和信号分子（KRAS, CD44， EGFR）的致癌外泌体（与非恶性外泌体相比有362种独特的蛋白质）的有价值的见解。据报道，致癌外泌体含有已知的调节转移前生态位的因子（S100A4, F3, ITG β 5, ANXA1），与预后不良相关的临床相关蛋白（CLDN1, MUC1）以及参与各种癌症标志的蛋白网络，包括增殖（CLU, CAV1），侵袭（PODXL, ITGA3），转移（LAMP1, ST14）和免疫监视逃避（B2M）。这些因子在致癌外泌体中的存在，有助于理解肿瘤发生过程中外泌体组成的选择性差异，以及胰腺癌预后和诊断生物标志物的潜在成分，并强调了外泌体在介导肿瘤和间质细胞之间的串扰中的作用。
Exosomes are small extracellular membrane vesicles important in intercellular communication, with their oncogenic cargo attributed to tumor progression and pre-metastatic niche formation. To gain an insight into key differences in oncogenic composition of exosomes, human non-malignant epithelial and pancreatic cancer cell models and purified and characterized resultant exosome populations are utilized. Proteomic analysis reveals the selective enrichment of known exosome markers and signaling proteins in comparison to parental cells. Importantly, valuable insights into oncogenic exosomes (362 unique proteins in comparison to non-malignant exosomes) of key metastatic regulatory factors and signaling molecules fundamental to pancreatic cancer progression (KRAS, CD44, EGFR) are provided. It is reported that oncogenic exosomes contain factors known to regulate the pre-metastatic niche (S100A4, F3, ITG beta 5, ANXA1), clinically-relevant proteins which correlate with poor prognosis (CLDN1, MUC1) as well as protein networks involved in various cancer hallmarks including proliferation (CLU, CAV1), invasion (PODXL, ITGA3), metastasis (LAMP1, ST14) and immune surveillance escape (B2M). The presence of these factors in oncogenic exosomes offers an understanding of select differences in exosome composition during tumorigenesis, potential components as prognostic and diagnostic biomarkers in pancreatic cancer, and highlights the role of exosomes in mediating crosstalk between tumor and stromal cells.