Pericyte depletion results in hypoxia-associated epithelial-to-mesenchymal transition and metastasis mediated by met signaling pathway.
Pericyte depletion results in hypoxia-associated epithelial-to-mesenchymal transition and metastasis mediated by met signaling pathway.
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DOI：
10.1016/j.ccr.2011.11.024
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发表时间：
2012-01-17
期刊：
影响因子：
50.3
通讯作者：
Kalluri R
中科院分区：
文献类型：
--
作者：
Cooke VG;LeBleu VS;Keskin D;Khan Z;O'Connell JT;Teng Y;Duncan MB;Xie L;Maeda G;Vong S;Sugimoto H;Rocha RM;Damascena A;Brentani RR;Kalluri R
周细胞在癌症进展中的功能作用尚不清楚。临床研究表明，低数量的血管相关周细胞与浸润性乳腺癌患者的总存活率下降有关。使用遗传小鼠模型或药物抑制剂，周细胞耗尽抑制了肿瘤的生长，但促进了转移。周细胞耗竭与缺氧增加、上皮向间充质转化(EMT)和Met受体激活进一步相关。沉默Twist或使用Met抑制剂可抑制缺氧和EMT/Met驱动的转移。此外，周细胞覆盖率低，加上癌细胞中Met的高表达，推测浸润性乳腺癌患者的预后最差。总而言之，我们的研究表明，原发肿瘤微环境中的周细胞可能是阻止癌症进展和转移的重要守门人。
The functional role of pericytes in cancer progression remains unknown. Clinical studies suggest that low numbers of vessel-associated pericytes correlated with a drop in overall survival of patients with invasive breast cancer. Using genetic mouse models or pharmacological inhibitors, pericyte depletion suppressed tumor growth but enhanced metastasis. Pericyte depletion was further associated with increased hypoxia, epithelial-to-mesenchymal transition (EMT), and Met receptor activation. Silencing of Twist or use of a Met inhibitor suppressed hypoxia and EMT/Met-driven metastasis. In addition, poor pericyte coverage coupled with high Met expression in cancer cells speculates the worst prognosis for patients with invasive breast cancer. Collectively, our study suggests that pericytes within the primary tumor microenvironment likely serve as important gatekeepers against cancer progression and metastasis.
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缺氧会增强乳腺癌中的 Notch 信号传导，导致 E-钙粘蛋白表达减少，细胞迁移和侵袭增加。
影响因子：
8.8
作者：
Chen, J.;Imanaka, N.;Chen, J.;Griffin, J. D.
通讯作者：
Griffin, J. D.
影响因子：
6
作者：
Baba, Yoshifumi;Nosho, Katsuhiko;Ogino, Shuji
通讯作者：
Ogino, Shuji
DOI：
10.1007/978-1-60761-938-3_2
发表时间：
2011-01-01
期刊：
BLOOD-BRAIN AND OTHER NEURAL BARRIERS: REVIEWS AND PROTOCOLS
影响因子：
--
作者：
Dore-Duffy, Paula;Cleary, Kristen
通讯作者：
Cleary, Kristen
影响因子：
--
作者：
Folkman, J
通讯作者：
Folkman, J
影响因子：
6.2
作者：
Bos, R;van der Groep, P;van der Wall, E
通讯作者：
van der Wall, E