Attenuation of TGF-β signaling supports tumor progression of a mesenchymal-like mammary tumor cell line in a syngeneic murine model.
Attenuation of TGF-β signaling supports tumor progression of a mesenchymal-like mammary tumor cell line in a syngeneic murine model.
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DOI：
10.1016/j.canlet.2013.12.018
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发表时间：
2014-04-28
期刊：
影响因子：
9.7
通讯作者：
Sun, Lu-Zhe
中科院分区：
文献类型：
--
作者：
Biswas, Tanuka;Gu, Xiang;Yang, Junhua;Ellies, Lesley G.;Sun, Lu-Zhe
先前的研究表明，TGF-β在转移性间充质样乳腺癌细胞中起肿瘤促进剂的作用，并且TGF-β抑制剂可以有效地消除这些模型中的几种模型中的肿瘤进展。在这里，我们报告了一个新的观察与使用遗传和药理学的方法，小鼠乳腺细胞注射模型在同基因和免疫受损的小鼠。我们发现，MMTV-PyMT衍生的Py 8119（一种间充质样小鼠乳腺肿瘤细胞系）中TGF-β受体II（TβRII）敲低导致同基因背景中原位肿瘤生长潜力增加，并在免疫受损背景中具有类似趋势。小分子TGF-β受体I激酶抑制剂的全身治疗诱导了Py 8119细胞心脏内接种后远处器官转移性定植增加的趋势，对同样来源于MMTV-PyMT肿瘤的管腔样Py 230细胞的定植几乎没有影响。总之，我们的数据表明，间充质样乳腺肿瘤中TGF-β信号传导的减弱不一定抑制其恶性潜能，抗TGF-β治疗干预需要更精确地鉴定具有功能性TGF-β信号传导指征的肿瘤中的分子标志物。
Previous studies have suggested that TGF-β functions as a tumor promoter in metastatic, mesenchymal-like breast cancer cells and that TGF-β inhibitors can effectively abrogate tumor progression in several of these models. Here we report a novel observation with the use of genetic and pharmacological approaches, and murine mammary cell injection models in both syngeneic and immune compromised mice. We found that TGF-β receptor II (TβRII) knockdown in the MMTV-PyMT derived Py8119, a mesenchymal-like murine mammary tumor cell line, resulted in increased orthotopic tumor growth potential in a syngeneic background and a similar trend in an immune compromised background. Systemic treatment with a small-molecule TGF-β receptor I kinase inhibitor induced a trend towards increased metastatic colonization of distant organs following intra cardiac inoculation of Py8119 cells, with little effect on the colonization of luminal-like Py230 cells, also derived from MMTV-PyMT tumors. Taken together, our data suggest that the attenuation of TGF-β signaling in mesenchymal-like mammary tumors does not necessarily inhibit their malignant potential, and anti-TGF-β therapeutic intervention requires greater precision in identifying molecular markers in tumors with an indication of functional TGF-β signaling.
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