Glycosylated extracellular vesicles released by glioblastoma cells are decorated by CCL18 allowing for cellular uptake via chemokine receptor CCR8.
Glycosylated extracellular vesicles released by glioblastoma cells are decorated by CCL18 allowing for cellular uptake via chemokine receptor CCR8.
复制标题
DOI：
10.1080/20013078.2018.1446660
复制
发表时间：
2018
影响因子：
16
通讯作者：
Wurdinger T
中科院分区：
文献类型：
--
作者：
Berenguer J;Lagerweij T;Zhao XW;Dusoswa S;van der Stoop P;Westerman B;de Gooijer MC;Zoetemelk M;Zomer A;Crommentuijn MHW;Wedekind LE;López-López À;Giovanazzi A;Bruch-Oms M;van der Meulen-Muileman IH;Reijmers RM;van Kuppevelt TH;García-Vallejo JJ;van Kooyk Y;Tannous BA;Wesseling P;Koppers-Lalic D;Vandertop WP;Noske DP;van Beusechem VW;van Rheenen J;Pegtel DM;van Tellingen O;Wurdinger T
癌细胞释放含有RNA和蛋白质等功能生物分子的胞外小泡(EV)。EVS被转移到受体癌细胞，并可以促进肿瘤进展和治疗耐药性。通过RNAi筛选，我们确定了一种新的EV摄取机制，涉及细胞上的趋化因子受体CCR8、EVS上暴露的多糖和可溶性配体CCL18之间的三重相互作用。这种配体起到桥梁分子的作用，将电动汽车与癌细胞连接起来。我们发现，胶质母细胞瘤EV促进细胞增殖和对烷化剂替莫唑胺(TMZ)的耐药性。使用体外和体内干状胶质母细胞瘤模型，我们证明EV诱导的表型可以被小分子CCR8抑制剂R243中和。干扰趋化因子受体可能提供治疗机会，以对抗EV介导的胶质母细胞瘤的串扰。
Cancer cells release extracellular vesicles (EVs) that contain functional biomolecules such as RNA and proteins. EVs are transferred to recipient cancer cells and can promote tumour progression and therapy resistance. Through RNAi screening, we identified a novel EV uptake mechanism involving a triple interaction between the chemokine receptor CCR8 on the cells, glycans exposed on EVs and the soluble ligand CCL18. This ligand acts as bridging molecule, connecting EVs to cancer cells. We show that glioblastoma EVs promote cell proliferation and resistance to the alkylating agent temozolomide (TMZ). Using in vitro and in vivo stem-like glioblastoma models, we demonstrate that EV-induced phenotypes are neutralised by a small molecule CCR8 inhibitor, R243. Interference with chemokine receptors may offer therapeutic opportunities against EV-mediated cross-talk in glioblastoma.
登录
查看更多内容
影响因子：
37.3
作者：
Beier D;Schulz JB;Beier CP
通讯作者：
Beier CP
影响因子：
56.9
作者：
COCCHI, F;DEVICO, AL;LUSSO, P
通讯作者：
LUSSO, P
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
影响因子：
64.8
作者：
Deng, HK;Liu, R;Landau, NR
通讯作者：
Landau, NR
影响因子：
3.7
作者：
Corcoran C;Rani S;O'Brien K;O'Neill A;Prencipe M;Sheikh R;Webb G;McDermott R;Watson W;Crown J;O'Driscoll L
通讯作者：
O'Driscoll L