Infiltrating neutrophils promote renal cell carcinoma (RCC) proliferation via modulating androgen receptor (AR) → c-Myc signals
Authors: Luke Sien-Shih Chang
Chawnshang Chang
Dalin He
Hongjun Xie
Chiuan-Ren Yeh
Lei Li
Shuyuan Yeh
Jiaqi Chen
Wenbin Song
Journal: Cancer letters (2015)
Discipline: CLINICAL MEDICINE
Keywords: Androgen receptor; Infiltrating neutrophils; Renal cell carcinoma (RCC); c-Myc signal.
Affiliations: Sex Hormone Research Center, Department of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China; George Whipple Lab for Cancer Research, Departments of Urology and Pathology, University of Rochester Medical Center, Rochester, New York 14642, USA., Sex Hormone Research Center, Department of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China. Electronic address: ., Sex Hormone Research Center, Department of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China., George Whipple Lab for Cancer Research, Departments of Urology and Pathology, University of Rochester Medical Center, Rochester, New York 14642, USA., George Whipple Lab for Cancer Research, Departments of Urology and Pathology, University of Rochester Medical Center, Rochester, New York 14642, USA; Sex Hormone Research Center, China Medical University and Hospital, Taichung, 404, Taiwan. Electronic address: .

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. 

Retracted: No

PubPeer comments:
 Figure 5B. * Blue boxes: The SW839 and SW839+Neu panels appear to show an overlap. ![file] , 
 Corrigendum, online May 2020: https: www.sciencedirect.com science article pii S0304383520302718  Due to an error while processing the figures the authors inserted the wrong images in the second microscopic image in Fig. 5b. The correct versions of the figures are presented below. The authors assure that these corrections do not change the original results and conclusions and apologize for the mistakes. ,