The Notch pathway is important in maintaining the cancer stem cell population in pancreatic cancer.
The Notch pathway is important in maintaining the cancer stem cell population in pancreatic cancer.
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DOI：
10.1371/journal.pone.0091983
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Simeone DM
中科院分区：
文献类型：
--
作者：
Abel EV;Kim EJ;Wu J;Hynes M;Bednar F;Proctor E;Wang L;Dziubinski ML;Simeone DM
胰腺癌干细胞（CSC）代表具有启动和增殖肿瘤形成能力的胰腺癌细胞的小亚群。然而，维持胰腺CSC的机制尚未得到很好的理解或表征。在来自8个原代人胰腺异种移植物的CSC和非CSC群体中定量Notch受体、配体和Notch信号传导靶基因的表达。使用抑制Notch途径的γ分泌酶抑制剂（GSI）和靶向Notch靶基因Hes 1的shRNA来评估Notch途径在CSC群体维持和胰腺肿瘤生长中的作用。Notch途径组分在胰腺CSC中被发现上调。在胰腺癌细胞中使用γ分泌酶抑制剂或Hes 1 shRNA抑制Notch途径降低了CSC和肿瘤球形成的百分比。相反，用外源性Notch肽配体激活Notch途径增加了CSC的百分比以及肿瘤球形成。用GSI在NOD/SCID小鼠中体内治疗原位胰腺肿瘤阻断了肿瘤生长并减少了CSC群体。Notch信号通路在维持胰腺CSC群体中是重要的，并且是胰腺癌的潜在治疗靶点。
Pancreatic cancer stem cells (CSCs) represent a small subpopulation of pancreatic cancer cells that have the capacity to initiate and propagate tumor formation. However, the mechanisms by which pancreatic CSCs are maintained are not well understood or characterized. Expression of Notch receptors, ligands, and Notch signaling target genes was quantitated in the CSC and non-CSC populations from 8 primary human pancreatic xenografts. A gamma secretase inhibitor (GSI) that inhibits the Notch pathway and a shRNA targeting the Notch target gene Hes1 were used to assess the role of the Notch pathway in CSC population maintenance and pancreatic tumor growth. Notch pathway components were found to be upregulated in pancreatic CSCs. Inhibition of the Notch pathway using either a gamma secretase inhibitor or Hes1 shRNA in pancreatic cancer cells reduced the percentage of CSCs and tumorsphere formation. Conversely, activation of the Notch pathway with an exogenous Notch peptide ligand increased the percentage of CSCs as well as tumorsphere formation. In vivo treatment of orthotopic pancreatic tumors in NOD/SCID mice with GSI blocked tumor growth and reduced the CSC population. The Notch signaling pathway is important in maintaining the pancreatic CSC population and is a potential therapeutic target in pancreatic cancer.
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DOI：
10.1186/bcr920
发表时间：
2004
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Dontu G;Jackson KW;McNicholas E;Kawamura MJ;Abdallah WM;Wicha MS
通讯作者：
Wicha MS
影响因子：
11.2
作者：
Charafe-Jauffret E;Ginestier C;Iovino F;Wicinski J;Cervera N;Finetti P;Hur MH;Diebel ME;Monville F;Dutcher J;Brown M;Viens P;Xerri L;Bertucci F;Stassi G;Dontu G;Birnbaum D;Wicha MS
通讯作者：
Wicha MS
影响因子：
64.8
作者：
Apelqvist, Å;Li, H;Edlund, H
通讯作者：
Edlund, H
影响因子：
64.8
作者：
O'Brien, Catherine A.;Pollett, Aaron;Dick, John E.
通讯作者：
Dick, John E.
影响因子：
11.2
作者：
Li, Chenwei;Heidt, David G.;Simeone, Diane M.
通讯作者：
Simeone, Diane M.