Exosomal zinc transporter ZIP4 promotes cancer growth and is a novel diagnostic biomarker for pancreatic cancer.
Exosomal zinc transporter ZIP4 promotes cancer growth and is a novel diagnostic biomarker for pancreatic cancer.
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DOI：
10.1111/cas.13737
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发表时间：
2018-09
期刊：
影响因子：
5.7
通讯作者：
Tan X
中科院分区：
文献类型：
--
作者：
Jin H;Liu P;Wu Y;Meng X;Wu M;Han J;Tan X
胰腺癌是最致命的癌症之一，具有快速的疾病进展。进一步阐明其潜在的分子机制和新的生物标志物的早期检测是必要的。外泌体是由多种细胞类型释放的小的细胞外囊泡，其在细胞间通讯期间充当信息载体，并且是有希望的生物标志物候选物。然而，胰腺癌细胞来源的外泌体在癌症进展中的作用以及这些囊泡作为新型诊断生物标志物的应用尚未得到充分研究。在这项研究中，我们发现PC-1.0（一种高度恶性的胰腺细胞系）细胞来源的外泌体可以被PC-1（一种中度恶性的胰腺细胞系）细胞吸收并增强PC-1（一种中度恶性的胰腺细胞系）细胞的增殖、迁移和侵袭能力。我们从我们的蛋白质组学分析中鉴定出ZIP 4是PC-1.0细胞中上调最多的外泌体蛋白。体外和体内（皮下BALB/c裸鼠模型）研究表明，外泌体ZIP 4可显著促进胰腺癌生长。使用临床血液样品，我们比较了恶性胰腺癌患者（n = 24）和良性胰腺疾病患者（n = 32，AUC = .89）之间以及胆道疾病患者（n = 32，AUC = .8112）和健康对照（n = 46，AUC = .8931）之间血清外泌体ZIP 4水平的诊断价值。总之，外泌体ZIP 4促进癌症生长，是胰腺癌的一种新的诊断生物标志物。
Pancreatic cancer is one of the deadliest cancers with rapid disease progression. Further elucidation of its underlying molecular mechanisms and novel biomarkers for early detection is necessary. Exosomes are small extracellular vesicles that are released by multiple cell types acting as message carriers during intercellular communication and are promising biomarker candidates. However, the role of pancreatic cancer cell‐derived exosomes in cancer progression and the application of these vesicles as novel diagnostic biomarkers have not been fully studied. In this study, we found that PC‐1.0 (a highly malignant pancreatic cell line) cell‐derived exosomes could be taken up by and enhance PC‐1 (a moderately malignant pancreatic cell line) cell proliferation, migration and invasion abilities. We identified ZIP4 as the most upregulated exosomal protein in PC‐1.0 cells from our proteomic analysis. In vitro and in vivo (a subcutaneous BALB/c nude mouse model) studies showed that exosomal ZIP4 can significantly promote pancreatic cancer growth. Using clinical blood samples, we compared the diagnostic values of serum exosomal ZIP4 levels between malignant pancreatic cancer patients (n = 24) and benign pancreatic disease patients (n = 32, AUC = .89), and between biliary disease patients (n = 32, AUC = .8112) and healthy controls (n = 46, AUC = .8931). In conclusion, exosomal ZIP4 promotes cancer growth and is a novel diagnostic biomarker for pancreatic cancer.
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影响因子：
7.3
作者：
Gao J;Aksoy BA;Dogrusoz U;Dresdner G;Gross B;Sumer SO;Sun Y;Jacobsen A;Sinha R;Larsson E;Cerami E;Sander C;Schultz N
通讯作者：
Schultz N
影响因子：
21.3
作者：
Costa-Silva B;Aiello NM;Ocean AJ;Singh S;Zhang H;Thakur BK;Becker A;Hoshino A;Mark MT;Molina H;Xiang J;Zhang T;Theilen TM;García-Santos G;Williams C;Ararso Y;Huang Y;Rodrigues G;Shen TL;Labori KJ;Lothe IM;Kure EH;Hernandez J;Doussot A;Ebbesen SH;Grandgenett PM;Hollingsworth MA;Jain M;Mallya K;Batra SK;Jarnagin WR;Schwartz RE;Matei I;Peinado H;Stanger BZ;Bromberg J;Lyden D
通讯作者：
Lyden D
ZIP4 是神经胶质瘤的新型分子标记。
影响因子：
15.9
作者：
Lin, Yi;Chen, Yong;Li, Min
通讯作者：
Li, Min
影响因子：
50.3
作者：
Becker A;Thakur BK;Weiss JM;Kim HS;Peinado H;Lyden D
通讯作者：
Lyden D
影响因子：
4.6
作者：
Liu P;Weng Y;Sui Z;Wu Y;Meng X;Wu M;Jin H;Tan X;Zhang L;Zhang Y
通讯作者：
Zhang Y