Tumor-promoting effects of pancreatic cancer cell exosomes on THP-1-derived macrophages.
Tumor-promoting effects of pancreatic cancer cell exosomes on THP-1-derived macrophages.
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DOI：
10.1371/journal.pone.0206759
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Matters GL
中科院分区：
文献类型：
--
作者：
Linton SS;Abraham T;Liao J;Clawson GA;Butler PJ;Fox T;Kester M;Matters GL
胰腺导管腺癌（PDAC）肿瘤生长受到肿瘤相关巨噬细胞（tam）的促进，但肿瘤细胞与tam之间的交流机制尚不完全清楚。本研究表明，PDAC细胞系分泌的外泌体在其表面蛋白、脂质组成以及与thp -1来源的巨噬细胞的体外融合效率方面存在差异。来自asc -1（一种源自腹水的人PDAC细胞系）的外泌体富含ICAM-1， ICAM-1通过与巨噬细胞表面暴露的CD11c相互作用介导其与巨噬细胞的对接。AsPC-1外泌体也含有更高水平的花生四烯酸（AA），它们与thp -1来源的巨噬细胞的融合率高于其他PDAC细胞系或永活正常胰腺导管上皮细胞系（HPDE） H6c7。磷脂酶A2从AsPC-1外泌体中切割花生四烯酸降低了融合效率。用AsPC-1外泌体处理的巨噬细胞中，PGE2分泌升高，而用其他细胞系外泌体处理的巨噬细胞中，PGE2分泌没有升高，这表明AsPC-1外泌体递送的花生四烯酸在巨噬细胞中发挥了功能作用。用AsPC-1外泌体处理的非极化（M0）巨噬细胞表面标记物水平升高，表明极化为免疫抑制的m2样表型（CD14hi、CD163hi、CD206hi）。此外，经AsPC-1外泌体处理的巨噬细胞显著增加了促肿瘤、生物活性分子的分泌，包括VEGF、MCP-1、IL-6、IL-1β、MMP-9和TNFα。总之，这些结果表明，与来自其他原发性肿瘤来源的PDAC细胞系的外泌体相比，AsPC-1外泌体改变了thp -1来源的巨噬细胞的表型和功能。AsPC-1外泌体介导肿瘤细胞和tam之间的通讯，促进肿瘤进展。
Pancreatic ductal adenocarcinoma (PDAC) tumor growth is enhanced by tumor-associated macrophages (TAMs), yet the mechanisms by which tumor cells and TAMs communicate are not fully understood. Here we show that exosomes secreted by PDAC cell lines differed in their surface proteins, lipid composition, and efficiency of fusing with THP-1-derived macrophages in vitro. Exosomes from AsPC-1, an ascites-derived human PDAC cell line, were enriched in ICAM-1, which mediated their docking to macrophages through interactions with surface-exposed CD11c on macrophages. AsPC-1 exosomes also contained much higher levels of arachidonic acid (AA), and they fused at a higher rate with THP-1-derived macrophages than did exosomes from other PDAC cell lines or from an immortalized normal pancreatic ductal epithelial cell line (HPDE) H6c7. Phospholipase A2 enzymatic cleavage of arachidonic acid from AsPC-1 exosomes reduced fusion efficiency. PGE2 secretion was elevated in macrophages treated with AsPC-1 exosomes but not in macrophages treated with exosomes from other cell lines, suggesting a functional role for the AsPC-1 exosome-delivered arachidonic acid in macrophages. Non-polarized (M0) macrophages treated with AsPC-1 exosomes had increased levels of surface markers indicative of polarization to an immunosuppressive M2-like phenotype (CD14hi CD163hi CD206hi). Furthermore, macrophages treated with AsPC-1 exosomes had significantly increased secretion of pro-tumoral, bioactive molecules including VEGF, MCP-1, IL-6, IL-1β, MMP-9, and TNFα. Together, these results demonstrate that compared to exosomes from other primary tumor-derived PDAC cell lines, AsPC-1 exosomes alter THP-1-derived macrophage phenotype and function. AsPC-1 exosomes mediate communication between tumor cells and TAMs that contributes to tumor progression.
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影响因子：
4.6
作者：
Hiraide T;Ikegami K;Sakaguchi T;Morita Y;Hayasaka T;Masaki N;Waki M;Sugiyama E;Shinriki S;Takeda M;Shibasaki Y;Miyazaki S;Kikuchi H;Okuyama H;Inoue M;Setou M;Konno H
通讯作者：
Konno H
DOI：
10.1073/pnas.1521230113
发表时间：
2016-02-23
影响因子：
11.1
作者：
Kowal, Joanna;Arras, Guillaume;Thery, Clotilde
通讯作者：
Thery, Clotilde
影响因子：
--
作者：
Golan, Talia;Stossel, Chani;Berger, Raanan
通讯作者：
Berger, Raanan
影响因子：
7.2
作者：
Javeed, Naureen;Gustafson, Michael P.;Mukhopadhyay, Debabrata
通讯作者：
Mukhopadhyay, Debabrata
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