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Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Oncotarget 2015 ; 6 (22): 19290-304 Nephropedia Template TP
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Infiltrating neutrophils promote renal cell carcinoma progression via VEGFa/HIF2? and estrogen receptor ? signals #MMPMID26079540
Song W; Yeh CR; He D; Wang Y; Xie H; Pang ST; Chang LSS; Li L; Yeh S
Oncotarget 2015[Aug]; 6 (22): 19290-304 PMID26079540show ga
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?, VEGFa and HIF2? mRNA levels. ER? signals increased RCC cell migration via induction of the VEGFa/HIF2? pathway. Treatment of HIF inhibitor or rapamycin, or knockdown of ER? 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?, VEGFa and HIF2? 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.