TGF-β and the Tissue Microenvironment: Relevance in Fibrosis and Cancer.
TGF-β and the Tissue Microenvironment: Relevance in Fibrosis and Cancer.
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DOI：
10.3390/ijms19051294
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发表时间：
2018-04-26
影响因子：
5.6
通讯作者：
Fabregat I
中科院分区：
文献类型：
--
作者：
Caja L;Dituri F;Mancarella S;Caballero-Diaz D;Moustakas A;Giannelli G;Fabregat I
转化生长因子-β（TGF-β）是诱导纤维化反应和活化癌间质所必需的细胞因子。强有力的证据表明，TGF-β和组织细胞外基质成分之间存在强烈的串扰。TGF-β作为与潜在TGF-β结合蛋白（LTBP）结合的大型潜在复合物的一部分储存在基质中，并与潜在TGF-β复合物的基质结合，这是充分发挥TGF-β功能所必需的。一旦TGF-β被激活，它调节细胞外基质重塑并促进成纤维细胞向肌成纤维细胞的转变，这在纤维化过程中是必不可少的。这种细胞因子还作用于纤维化和肿瘤微环境中存在的其他细胞类型，例如上皮细胞、内皮细胞或巨噬细胞，并且它有助于癌症相关成纤维细胞（CAF）表型。此外，TGF-β通过抑制宿主肿瘤免疫监视发挥抗肿瘤活性。这篇综述的目的是更新TGF-β和组织微环境如何合作，以促进调节不同细胞类型的细胞反应的多效性作用，这对纤维化和肿瘤进展的发展至关重要。我们讨论了最近的证据表明，使用TGF-β化学抑制剂作为一种新的防线，对纤维化疾病或癌症。
Transforming growth factor-β (TGF-β) is a cytokine essential for the induction of the fibrotic response and for the activation of the cancer stroma. Strong evidence suggests that a strong cross-talk exists among TGF-β and the tissue extracellular matrix components. TGF-β is stored in the matrix as part of a large latent complex bound to the latent TGF-β binding protein (LTBP) and matrix binding of latent TGF-β complexes, which is required for an adequate TGF-β function. Once TGF-β is activated, it regulates extracellular matrix remodelling and promotes a fibroblast to myofibroblast transition, which is essential in fibrotic processes. This cytokine also acts on other cell types present in the fibrotic and tumour microenvironment, such as epithelial, endothelial cells or macrophages and it contributes to the cancer-associated fibroblast (CAF) phenotype. Furthermore, TGF-β exerts anti-tumour activity by inhibiting the host tumour immunosurveillance. Aim of this review is to update how TGF-β and the tissue microenvironment cooperate to promote the pleiotropic actions that regulate cell responses of different cell types, essential for the development of fibrosis and tumour progression. We discuss recent evidences suggesting the use of TGF-β chemical inhibitors as a new line of defence against fibrotic disorders or cancer.
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作者：
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影响因子：
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DOI：
10.1073/pnas.0408197102
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