Elevated DLL3 in stomach cancer by tumor-associated macrophages enhances cancer-cell proliferation and cytokine secretion of macrophages.
Elevated DLL3 in stomach cancer by tumor-associated macrophages enhances cancer-cell proliferation and cytokine secretion of macrophages.
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通过肿瘤相关的巨噬细胞在胃癌中升高DLL3可增强巨噬细胞的癌细胞增殖和细胞因子分泌。
DOI:
10.1093/gastro/goab052
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发表时间:
2022
影响因子:
3.6
通讯作者:
Li Y
中科院分区:
文献类型:
--
作者:
Ye JB;Wen JJ;Wu DL;Hu BX;Luo MQ;Lin YQ;Ning YS;Li Y
The notch signal pathway is important in the development of both tumor-associated macrophages (TAMs) and stomach cancer, but how Notch signaling affects TAMs in stomach cancer is barely understood. The expressions of Notch1, Notch2, Notch3, Notch4, hes family bHLH transcription factor 1 (Hes1), and delta-like canonical Notch ligand 3 (DLL3) were detected by Western blot and the expressions of interleukin (IL)-10, IL-12, and IL1-β were detected using enzyme-linked immunosorbent assay after the co-culture of macrophages and stomach-cancer cells. The proliferation and migration of cancer cells were detected using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and scratch assay, respectively, and the cell cycle was detected using Annexin V/propidium iodide assay. The protein interactions with DLL3 were detected using co-immunoprecipitation and mass spectrometry. The co-culture of macrophages and stomach-cancer cells MKN45 and BGC823 could enhance cell proliferation accompanied by the activation of Notch1/Notch2 signaling and upregulation of DLL3. Notch signaling gamma-secretase inhibitor (DAPT) blocked this process. The overexpression of DLL3 in stomach-cancer cells could promote the proliferation of cancer cells, enhance the activation of Notch1/Notch2 signaling, induce the expression of IL-33, lead to the degradation of galectin-3–binding protein (LG3BP) and heat shock cognate 71 kDa protein (HSPA8), and result in elevated IL-1β, IL-12, and IL-10 secretion by macrophages. Higher expression of DLL3 or IL-33 could lead to a lower survival rate based on University of California, Santa Cruz Xena Functional Genomics Explorer and The Cancer Genome Atlas data set. This is evidence that DLL3 regulates macrophages in stomach cancer, suggesting that DLL3 may be a novel and potential target for stomach-cancer therapy.
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影响因子:
5.3
作者:
Jiang L;Lin T;Xu C;Hu S;Pan Y;Jin R
通讯作者:
Jin R
DOI:
10.1083/jcb.200702009
发表时间:
2007-07-30
期刊:
The Journal of cell biology
影响因子:
--
作者:
Geffers I;Serth K;Chapman G;Jaekel R;Schuster-Gossler K;Cordes R;Sparrow DB;Kremmer E;Dunwoodie SL;Klein T;Gossler A
通讯作者:
Gossler A
影响因子:
24.5
作者:
Gifford GB;Demitrack ES;Keeley TM;Tam A;La Cunza N;Dedhia PH;Spence JR;Simeone DM;Saotome I;Louvi A;Siebel CW;Samuelson LC
通讯作者:
Samuelson LC
影响因子:
3.8
作者:
Li S;Wang W;Zhang N;Ma T;Zhao C
通讯作者:
Zhao C
影响因子:
3.8
作者:
Liu, Hang;Wang, Jingxuan;Zhang, Qingyuan
通讯作者:
Zhang, Qingyuan