Tumor cell-specific blockade of CXCR4/SDF-1 interactions in prostate cancer cells by hTERT promoter induced CXCR4 knockdown: A possible metastasis preventing and minimizing approach

• DOI: 10.4161/cbt.7.11.6862
• Publication Date: 2010-12-28T21:44:02Z
• Authors: Yifei Xing; Mei Liu; Yuefeng Du; Feng Qu; Yangsheng Li; Qingwei Zhang; Yajun Xiao; Jun Zhao; Fuqing Zeng; Chuanguo Xiao
• Keywords: Male; 0301 basic medicine; Receptors, CXCR4; Models, Genetic; Prostatic Neoplasms; Chemokine CXCL12; 3. Good health; Gene Expression Regulation, Neoplastic; 03 medical and health sciences; Cell Movement; Cell Line, Tumor; Cell Adhesion; Humans; Neoplasm Invasiveness; Neoplasm Metastasis; Promoter Regions, Genetic; Telomerase

Abstracttromal cell-derived factor-1 (SDF-1)/CXCR4 pathway has been shown to play an important role in prostate cancer (PCa) metastasis and siRNA expression using cell-specific promoters demonstrated be a potential tool for targeted gene therapy. Here, we illustrate that human telomerase reverse transcriptase (hTERT) promoter-induced CXCR4 knockdown inhibits PCa bone metastasis. We first investigated expressions interactions of CXCR4/SDF-1 cells, developed retrovirus system could stably express small hairpin RNA driven by hTERT promoter then determined the inhibitory effects blockade on It was both tissues cell lines expressed tissue had positive correlation clinical stages while not Gleason scores or serum PSA level. metastases most presenting high levels SDF-1. Exogenous SDF-1 enhanced vitro adhesion, migration invasion cells these bioeffects were repressed CXCR4- shRNA expression. This also found significantly inhibit vivo. conclude plays tumor silencing may prevent invasiveness vivo PCa. These findings enable new avenues prevention treatment