Hyperoxic treatment induces mesenchymal-to-epithelial transition in a rat adenocarcinoma model.
Hyperoxic treatment induces mesenchymal-to-epithelial transition in a rat adenocarcinoma model.
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DOI：
10.1371/journal.pone.0006381
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发表时间：
2009-07-28
期刊：
影响因子：
3.7
通讯作者：
Stuhr LE
中科院分区：
文献类型：
--
作者：
Moen I;Øyan AM;Kalland KH;Tronstad KJ;Akslen LA;Chekenya M;Sakariassen PØ;Reed RK;Stuhr LE
肿瘤缺氧与肿瘤生长、代谢和上皮-间质转化（EMT）有关。我们报道高压氧（HBO）治疗在二甲基-α-苯并蒽诱导的大鼠乳腺癌模型中诱导间质-上皮转化（MET），MET与广泛的协调基因表达变化和较低侵袭性肿瘤相关。一组荷瘤大鼠暴露于HBO（2 bar，pO 2 = 2 bar，4次暴露，90分钟），而对照组饲养在正常大气（1 bar，pO 2 = 0.2 bar）下。 通过评估肿瘤生长、肿瘤血管形成、肿瘤细胞增殖、细胞死亡、胶原纤维和基因表达谱来确定治疗效果。与第1天的水平相比，HBO治疗后肿瘤生长显著减少（约16%），而对照肿瘤体积几乎增加100%。肿瘤细胞增殖、肿瘤血管和胶原纤维的显著减少以及细胞死亡的增加与高氧治疗后肿瘤生长减少和肿瘤间质影响一致。基因表达谱分析表明，HBO诱导MET。总之，高氧诱导MET与参与细胞连接和附着的基因模块的协调表达以及向非致瘤性代谢的转变。这导致更多的分化和更少的侵略性肿瘤，并表明，氧气本身可能是一个重要的因素，在体内的EMT和MET的“开关”。HBO治疗还通过靶向血管系统来减弱肿瘤生长并改变肿瘤基质，具有抗增殖和促凋亡作用。
Tumor hypoxia is relevant for tumor growth, metabolism and epithelial-to-mesenchymal transition (EMT). We report that hyperbaric oxygen (HBO) treatment induced mesenchymal-to-epithelial transition (MET) in a dimetyl-α-benzantracene induced mammary rat adenocarcinoma model, and the MET was associated with extensive coordinated gene expression changes and less aggressive tumors. One group of tumor bearing rats was exposed to HBO (2 bar, pO2 = 2 bar, 4 exposures à 90 minutes), whereas the control group was housed under normal atmosphere (1 bar, pO2 = 0.2 bar). Treatment effects were determined by assessment of tumor growth, tumor vascularisation, tumor cell proliferation, cell death, collagen fibrils and gene expression profile. Tumor growth was significantly reduced (∼16%) after HBO treatment compared to day 1 levels, whereas control tumors increased almost 100% in volume. Significant decreases in tumor cell proliferation, tumor blood vessels and collagen fibrils, together with an increase in cell death, are consistent with tumor growth reduction and tumor stroma influence after hyperoxic treatment. Gene expression profiling showed that HBO induced MET. In conclusion, hyperoxia induced MET with coordinated expression of gene modules involved in cell junctions and attachments together with a shift towards non-tumorigenic metabolism. This leads to more differentiated and less aggressive tumors, and indicates that oxygen per se might be an important factor in the “switches” of EMT and MET in vivo. HBO treatment also attenuated tumor growth and changed tumor stroma, by targeting the vascular system, having anti-proliferative and pro-apoptotic effects.
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N-钙粘着蛋白在乳腺癌细胞中的外源表达会诱导细胞迁移，侵袭和转移。
影响因子：
7.8
作者：
Hazan, R B;Phillips, G R;Qiao, R F;Norton, L;Aaronson, S A
通讯作者：
Aaronson, S A
影响因子：
2.9
作者：
Hopf, HW;Gibson, JJ;Hunt, TK
通讯作者：
Hunt, TK
影响因子：
2.7
作者：
Chaffer, Christine L.;Thompson, Erik W.;Williams, Elizabeth D.
通讯作者：
Williams, Elizabeth D.
影响因子：
8.4
作者：
Milani, Manuela;Harris, Adrian L.
通讯作者：
Harris, Adrian L.
胶原蛋白结合蛋白多糖纤维蛋白可确定实验性癌症的基质结构和体液平衡
DOI：
10.1073/pnas.0702014104
发表时间：
2007-08-28
影响因子：
11.1
作者：
Oldberg, Ake;Kalamajski, Sebastian;Rubin, Kristofer
通讯作者：
Rubin, Kristofer