キタハラ　シユウジ   Kitahara Shiyuuji   北原　秀治    所属   医学研究科 医学研究科 (医学部医学科をご参照ください)    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