Zhifu Liu , Yuxuan Tian , Zheng Li , Zhen Li , Kehao Yang , Yiming Zeng , Jiao Hu , Yuanwei Li , Xiongbing Zu , Shuai Hu
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引用次数: 0
Abstract
The role of immune cells, particularly neutrophils, in the prostate cancer (PCa) progression remains poorly understood. In this study, we investigated the impact of neutrophils on PCa progression using an in vitro co-culture migration assay. Our findings revealed that PCa cells recruited more neutrophils than normal prostate epithelial cells. Importantly, the recruitment of neutrophils to PCa cells led to increased PCa cell proliferation. Further mechanistic investigations revealed that co-culture of PCa cells with neutrophils led to increased secretion of the chemokine CXCL1. This, in turn, stimulated neutrophils to produce the cytokine IL-8. The enhanced CXCL1/IL-8 signaling axis subsequently amplified androgen receptor (AR) signaling in PCa cells, thereby promoting their proliferation. Disruption of this pathway via IL-8 neutralizing antibodies or AR knockdown reversed the neutrophil-induced PCa cell proliferation. These findings were validated in a mouse model and further supported by clinical sample analysis. Collectively, our study highlights the therapeutic potential of targeting the newly identified signaling cascade involving infiltrating neutrophils within the PCa microenvironment. Understanding and modulating this pathway may offer novel strategies to suppress PCa progression.
期刊介绍:
Our scope includes but is not limited to areas such as: Chromosome biology; Chromatin and epigenetics; DNA repair; Gene regulation; Nuclear import-export; RNA processing; Non-coding RNAs; Organelle biology; The cytoskeleton; Intracellular trafficking; Cell-cell and cell-matrix interactions; Cell motility and migration; Cell proliferation; Cellular differentiation; Signal transduction; Programmed cell death.