Transforming growth factor beta (TGF-beta) and inflammation in cancer.
Transforming growth factor beta (TGF-beta) and inflammation in cancer.
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DOI：
10.1016/j.cytogfr.2009.11.008
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发表时间：
2010-02
影响因子：
13
通讯作者：
Moses, Harold L.
中科院分区：
文献类型：
--
作者：
Bierie, Brian;Moses, Harold L.
转化生长因子β（TGF-β）在调节细胞行为方面的研究已经超过三十年。大量的研究致力于体外和体内上皮细胞和衍生癌细胞群体的调节。已显示TGF-β抑制上皮细胞周期进展并促进细胞凋亡，这两者一起显著有助于TGF-β在癌起始和进展期间的肿瘤抑制作用。然而，TGF-β还能够促进上皮向间充质转化，其与增加的肿瘤细胞运动性、侵袭和转移相关。然而，现在已经表明，癌细胞对TGF-β刺激的反应性的丧失也可以促进转移。有趣的是，在不存在癌细胞对TGF-β刺激的应答的情况下，转移的增强已被证明涉及增加的趋化因子产生，导致促转移性髓源性抑制细胞（MDSC）群体在前沿侵入边缘处募集到肿瘤微环境中。当存在时，MDSC增强血管生成，促进免疫耐受并提供促进肿瘤进展和转移的基质降解酶。此外，在这种情况下，MDSC群的募集可能增强TGF-β在免疫抑制中的经典作用，因为MDSC是TGF-β产生的丰富来源。重要的是，现在清楚的是，由癌细胞内的TGF-β信号传导引发的癌-免疫细胞串扰是在设计治疗策略以管理肿瘤进展和转移时值得考虑的重要决定因素。
The transforming growth factor beta (TGF-β) has been studied with regard to the regulation of cell behavior for over three decades. A large body of research has been devoted to the regulation of epithelial cell and derivative carcinoma cell populations in vitro and in vivo. TGF-β has been shown to inhibit epithelial cell cycle progression and promote apoptosis that together significantly contribute to the tumor suppressive role for TGF-β during carcinoma initiation and progression. However, TGF-β is also able to promote an epithelial to mesenchymal transition that has been associated with increased tumor cell motility, invasion and metastasis. However, it has now been shown that loss of carcinoma cell responsiveness to TGF-β stimulation can also promote metastasis. Interestingly, the enhanced metastasis in the absence of a carcinoma cell response to TGF-β stimulation has been shown to involve increased chemokine production resulting in recruitment of pro-metastatic myeloid derived suppressor cell (MDSC) populations to the tumor microenvironment at the leading invasive edge. When present, MDSCs enhance angiogenesis, promote immune tolerance and provide matrix degrading enzymes that promote tumor progression and metastasis. Further, the recruitment of MDSC populations in this context likely enhances the classic role for TGF-β in immune suppression since the MDSCs are an abundant source of TGF-β production. Importantly, it is now clear that carcinoma-immune cell cross-talk initiated by TGF-β signaling within the carcinoma cell is a significant determinant worth consideration when designing therapeutic strategies to manage tumor progression and metastasis.
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影响因子：
2.8
作者：
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通讯作者：
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影响因子：
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发表时间：
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影响因子：
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作者：
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通讯作者：
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影响因子：
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