Infiltrating neutrophils promote renal cell carcinoma (RCC) proliferation via modulating androgen receptor (AR) → c-Myc signals. Issue 1 (1st November 2015)

• Record Type: Journal Article
• Authors: Song, Wenbin; Li, Lei; He, Dalin; Xie, Hongjun; Chen, Jiaqi; Yeh, Chiuan-Ren; Chang, Luke Sien-Shih; Yeh, Shuyuan; Chang, Chawnshang
• Is Part Of: Cancer letters. Volume 368:Issue 1(2016)
• Page Start: 71
• Page End: 78
• Publication Date: 2015-11-01
• Subjects: Infiltrating neutrophils -- Renal cell carcinoma (RCC) -- Androgen receptor -- c-Myc signal; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.canlet.2015.07.027
• Languages: English
• ISSNs: 0304-3835

Abstract

Highlights: Renal cell carcinoma (RCC) could recruit more neutrophils than normal kidney tissues. Infiltrated neutrophils could promote RCC proliferation in vitro and in vivo . Infiltrated neutrophils may function through modulation of the AR → c-Myc signals to promote RCC cell proliferation. Abstract: Early studies found critical roles for neutrophils in renal cell carcinoma (RCC) progression. However, detailed mechanisms of how infiltrating neutrophils in the kidney tumor microenvironment impact RCC progression remain unclear. Here we found more neutrophils were infiltrated in human RCC lesions than those found in surrounding normal kidney tissues. Similarly, in vitro studies also revealed that RCC cells recruited more neutrophil HL-60N cells than normal kidney epithelial cells. Furthermore, in vitro and in vivo experiments also showed that the infiltrated neutrophils could promote RCC cell growth. Mechanism studies showed that co-culture of RCC cells with neutrophil HL-60N cells could selectively upregulate the androgen receptor (AR) signals, which might then alter the c-Myc signals. Interruption approaches using AR-siRNA to knock down AR in RCC cells blocked neutrophil-enhanced RCC cell proliferation. In vivo data using an orthotopically xenografted RCC mouse model also confirmed that infiltrated neutrophils could promote RCC proliferation via modulating the expressions of related cytokines. Together, these results conclude that infiltrated neutrophils may function through modulating the AR → c-Myc signals to promote RCC cell proliferation. Targeting this newly identified infiltrating neutrophil → AR → c-Myc signal pathway in the kidney tumor microenvironment may provide a new potential therapy to better suppress RCC progression.