Division of Matrix Biology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA 02115, USA.
Cancer Cell. 2012 Jan 17;21(1):66-81. doi: 10.1016/j.ccr.2011.11.024.
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.
周细胞在癌症进展中的功能作用尚不清楚。临床研究表明，血管相关周细胞数量减少与浸润性乳腺癌患者总体生存率下降相关。利用遗传小鼠模型或药理学抑制剂耗竭周细胞可抑制肿瘤生长，但促进转移。周细胞耗竭与缺氧、上皮间质转化（EMT）和 Met 受体激活增加进一步相关。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，原发性肿瘤微环境中周细胞覆盖不良，加上癌细胞中 Met 表达升高，推测浸润性乳腺癌患者预后最差。综上所述，我们的研究表明，原发性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员。
