キタハラ シユウジ   KITAHARA Shuji
  北原 秀治
   所属   研究施設 研究施設
   職種   特任准教授
論文種別 原著
言語種別 英語
査読の有無 査読あり
表題 Inhibition of CXCR4 Enhances the Efficacy of Radiotherapy in Metastatic Prostate Cancer Models.
掲載誌名 正式名:Cancers
略  称:Cancers (Basel)
ISSNコード:20726694/20726694
掲載区分国外
巻・号・頁 15(4),pp.1021
著者・共著者 GUPTA Nisha†, OCHIAI Hiroki, HOSHINO Yoshinori, KLEIN Sebastian, ZUSTIN Jozef, RAMJIAWAN Rakesh R, KITAHARA Shuji, MAIMON Nir, BAZOU Despina, CHIANG Sarah, LI Sen, SCHANNE Daniel H,, JAIN Rakesh K, MUNN Lance L, HUANG Peigen,, KOZIN Sergey V, DUDA Dan G
発行年月 2023/02
概要 Radiotherapy (RT) is a standard treatment for patients with advanced prostate cancer (PCa). Previous preclinical studies showed that SDF1α/CXCR4 axis could mediate PCa metastasis (most often to the bones) and cancer resistance to RT. We found high levels of expression for both SDF1α and its receptor CXCR4 in primary and metastatic PCa tissue samples. In vitro analyses using PCa cells revealed an important role of CXCR4 in cell invasion but not radiotolerance. Pharmacologic inhibition of CXCR4 using AMD3100 showed no efficacy in orthotopic primary and bone metastatic PCa models. However, when combined with RT, AMD3100 potentiated the effect of local single-dose RT (12 Gy) in both models. Moreover, CXCR4 inhibition also reduced lymph node metastasis from primary PCa. Notably, CXCR4 inhibition promoted the normalization of bone metastatic PCa vasculature and reduced tissue hypoxia. In conclusion, the SDF1α/CXCR4 axis is a potential therapeutic target in metastatic PCa patients treated with RT.
DOI 10.3390/cancers15041021
PMID 36831366