PDF(Pubmed)
Abstract：
Accumulating evidence shows that exosomes participate in cancer progression. However, the functions of cancer cell exosome-transmitted proteins are rarely studied. Previously, we reported that serglycin (SRGN) overexpression promotes invasion and metastasis of esophageal squamous cell carcinoma (ESCC) cells. Here, we investigated the paracrine effects of exosomes from SRGN-overexpressing ESCC cells (SRGN Exo) on ESCC cell invasion and tumor angiogenesis, and used mass spectrometry to identify exosomal proteins involved. Cation-dependent mannose-6-phosphate receptor (M6PR) and ephrin type-B receptor 4 (EphB4) were pronouncedly upregulated in SRGN Exo. Upregulated exosomal M6PR mediated the pro-angiogenic effects of SRGN Exo both in vitro and in vivo, while augmented exosomal EphB4 mediated the pro-invasive effect of SRGN Exo on ESCC cells in vitro. In addition, in vitro studies showed that manipulation of M6PR expression affected the viability and migration of ESCC cells. Both M6PR and EphB4 expression levels were positively correlated with that of SRGN in the serum of patients with ESCC. High level of serum M6PR was associated with poor overall survival rates. Taken together, this study presents the first proof that exosomal M6PR and EphB4 play essential roles in tumor angiogenesis and malignancy, and that serum M6PR is a novel prognostic marker for ESCC patients.
摘要：
越来越多的证据表明，外泌体参与癌症进展。然而,很少研究癌细胞外泌体传递蛋白的功能。以前,我们报道serglycin（SRGN）过表达促进食管鳞状细胞癌（ESCC）细胞的侵袭和转移。这里,我们研究了来自SRGN过表达ESCC细胞的外泌体（SRGNExo）对ESCC细胞侵袭和肿瘤血管生成的旁分泌作用，并使用质谱来鉴定所涉及的外来体蛋白。阳离子依赖性甘露糖-6-磷酸受体（M6PR）和ephrinB型受体4（EphB4）在SRGNExo中明显上调。上调的外泌体M6PR在体外和体内介导了SRGNExo的促血管生成作用，而增强的外泌体EphB4介导了SRGNExo对ESCC细胞的体外侵袭作用。此外,体外研究表明，M6PR表达的操纵会影响ESCC细胞的活力和迁移。ESCC患者血清中M6PR和EphB4的表达水平均与SRGN呈正相关。高水平的血清M6PR与低的总体生存率相关。一起来看,这项研究首次证明了外泌体M6PR和EphB4在肿瘤血管生成和恶性肿瘤中起着至关重要的作用，血清M6PR是ESCC患者的一种新的预后指标。
