The complexities of TGF-β action during mammary and squamous cell carcinogenesis.
The complexities of TGF-β action during mammary and squamous cell carcinogenesis.
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DOI：
10.2174/138920111798808284
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发表时间：
2011-12
影响因子：
2.8
通讯作者：
Akhurst RJ
中科院分区：
文献类型：
--
作者：
Connolly EC;Akhurst RJ
许多晚期肿瘤产生过量的转化生长因子-β（TGF-β），其是正常上皮细胞的有效生长抑制剂。然而，在肿瘤中，它对细胞的稳态作用可以沿着沿着几条替代途径转移。因此，据报道，TGF-β信号传导在肿瘤发生的早期阶段引起预防或肿瘤抑制作用，但在肿瘤发展的后期，当癌细胞变得对TGF-β介导的生长抑制不敏感时，对TGF-β信号传导的应答主要引起肿瘤进展作用。这不是一个简单的从抑制到进展的转换，而更像是一个变阻器，涉及多个互补和拮抗的活动，慢慢地从一个平衡到另一个平衡。本文就TGF-β在鳞状细胞癌和乳腺癌两种上皮性肿瘤中的作用机制进行综述。本文介绍了目前小鼠癌症模型的基本研究结果，并讨论了改变TGFβ信号转导的结果取决于小鼠品系之间的遗传变异性的复杂问题。本文还讨论了TGF-β在肿瘤微环境中的作用，特别是其将微环境转化为促肿瘤发生环境的能力。
Many advanced tumors produce excess amounts of Transforming Growth Factor-β (TGF-β), which is a potent growth inhibitor of normal epithelial cells. However, in tumors its homeostatic action on cells can be diverted along several alternative pathways. Thus, TGF-β signaling has been reported to elicit a preventative or tumor suppressive effect during the earlier stages of tumorigenesis, but later in tumor development, when carcinoma cells become refractory to TGF-β-mediated growth inhibition, response to TGF-β signaling elicits predominantly tumor progressing effects. This is not a simple switch from suppression to progression, but more like a rheostat, involving multiple complementary and antagonizing activities that slowly tip the balance from one to the other. This review will focus on the multiple activities of TGF-β in regulation of two epithelial tumor types, namely squamous cell carcinoma and breast cancer. Basic findings in current mouse models of cancer are presented, as well as a discussion of the complicating issue of outcome of altered TGFβ signaling depending on genetic variability between mouse strains. This review also discusses the role TGF-β within the tumor microenvironment particularly its ability to polarize the microenvironment towards a pro-tumorigenic milieu.