TNFα enhances cancer stem cell-like phenotype via Notch-Hes1 activation in oral squamous cell carcinoma cells.
TNFα enhances cancer stem cell-like phenotype via Notch-Hes1 activation in oral squamous cell carcinoma cells.
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DOI：
10.1016/j.bbrc.2012.06.065
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发表时间：
2012-07-20
影响因子：
3.1
通讯作者：
Shin KH
中科院分区：
文献类型：
--
作者：
Lee SH;Hong HS;Liu ZX;Kim RH;Kang MK;Park NH;Shin KH
癌干细胞样细胞（Cancer stem-样cell， CSC，又称肿瘤起始细胞）是肿瘤内的一小部分癌细胞亚群，从各种原发肿瘤和癌细胞系中分离出来。csc具有高度致瘤性，对抗癌治疗具有耐药性。在这项研究中，我们发现长时间暴露于肿瘤坏死因子α (TNFα)，一种主要的促炎细胞因子，增强了口腔鳞状细胞癌（OSCC）细胞的CSC表型，如肿瘤球体形成能力，干细胞相关基因表达，化学放射抗性和致瘤性的增加。此外，在tnf α暴露的细胞中检测到Notch1信号的激活，Notch1信号的抑制抑制了CSC表型。此外，我们证明了Notch下游靶点Hes-1的抑制导致tnf α-暴露细胞中CSC表型的抑制。我们还发现，与癌前发育不良病变相比，Hes1在OSCC病变中的表达普遍上调，这表明Hes1可能参与了体内OSCC的进展和CSC。综上所述，炎症细胞因子暴露可能通过激活Notch-Hes1通路来增强OSCC的CSC表型。
Cancer stem-like cell (CSC; also known as tumor initiating cell) is defined as a small subpopulation of cancer cells within a tumor and isolated from various primary tumors and cancer cell lines. CSCs are highly tumorigenic and resistant to anticancer treatments. In this study, we found that prolonged exposure to tumor necrosis factor alpha (TNFα), a major proinflammatory cytokine, enhances CSC phenotype of oral squamous cell carcinoma (OSCC) cells, such as an increase in tumor sphere-forming ability, stem cell-associated genes expression, chemo-radioresistance, and tumorigenicity. Moreover, activation of Notch1 signaling was detected in the TNFα-exposed cells, and suppression of Notch1 signaling inhibited CSC phenotype. Furthermore, we demonstrated that inhibition of a Notch downstream target, Hes-1, led to suppression of CSC phenotype in the TNFα-exposed cells. We also found that Hes1 expression is commonly upregulated in OSCC lesions compared to precancerous dysplastic lesions, suggesting the possible involvement of Hes1 in OSCC progression and CSC in vivo. In conclusion, inflammatory cytokine exposure may enhance CSC phenotype of OSCC, in part by activating the Notch-Hes1 pathway.
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影响因子：
11.5
作者：
Evangelista, Marie;Tian, Hua;de Sauvage, Frederic J.
通讯作者：
de Sauvage, Frederic J.
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：
5.6
作者：
Storci, Gianluca;Sansone, Pasquale;Mari, Sara;D'uva, Gabriele;Tavolari, Simona;Guarnieri, Tiziana;Taffurelli, Mario;Ceccarelli, Claudio;Santini, Donatella;Chieco, Pasquale;Marcu, Kenneth B.;Bonafe, Massimiliano
通讯作者：
Bonafe, Massimiliano
影响因子：
2.2
作者：
Johansson, T.;Lejonklou, M. H.;Skogseid, B.
通讯作者：
Skogseid, B.
DOI：
10.1186/bcr2106
发表时间：
2008
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Grimshaw MJ;Cooper L;Papazisis K;Coleman JA;Bohnenkamp HR;Chiapero-Stanke L;Taylor-Papadimitriou J;Burchell JM
通讯作者：
Burchell JM