期刊
ONCOTARGET
卷 6, 期 22, 页码 19290-19304出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.4478
关键词
tumor microenvironment; RCC; Neutrophils; ER beta; VEGF alpha and HIF pathways
Neutrophils make up a significant portion of the infiltrated immune cells found in the tumor microenvironment. Here we found more infiltrated neutrophils in human renal cell carcinoma (RCC) lesions than adjacent benign areas. In vitro RCC studies showed that neutrophils (HL-60N cells) infiltrated toward RCC cells and subsequently enhanced RCC cell migration and invasion. Co-culture of RCC cells with HL-60N cells up-regulated ER beta, VEGFa and HIF2 alpha mRNA levels. ER beta signals increased RCC cell migration via induction of the VEGFa/HIF2 alpha pathway. Treatment of HIF inhibitor or rapamycin, or knockdown of ER beta in RCC cells reversed HL-60N-promoted RCC migration. In vivo data using orthotopically xenografted RCC mouse model confirmed that infiltrated neutrophils promoted RCC migration via modulating the expressions of ER beta, VEGFa and HIF2 alpha signal pathways. Together, our studies revealed that neutrophils are favorably recruited to the RCC cells to promote the RCC migration and invasion. Targeting the infiltrating RCC tumor microenvironment with anti-estrogen or rapamycin may be a potential therapy to suppress RCC progression.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据