CXCR4 inhibition enhances radiosensitivity, while inducing cancer cell mobilization in a prostate cancer mouse model
CXCR4 inhibition enhances radiosensitivity, while inducing cancer cell mobilization in a prostate cancer mouse model
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DOI：
10.1007/s10585-014-9673-2
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发表时间：
2014-10-01
影响因子：
4
通讯作者：
Walenkamp, Annemiek M. E.
中科院分区：
文献类型：
--
作者：
Domanska, Urszula M.;Boer, Jennifer C.;Walenkamp, Annemiek M. E.
临床前研究表明，基质通过激活CXCR 4/CXCL 12通路影响前列腺癌细胞的敏感性。在这里，我们研究了CXCR 4抑制结合放射在前列腺癌细胞中的作用。在与基质细胞的体外共培养中，CXCR 4抑制剂AMD 3100使前列腺癌细胞系PC 3-Luc和LNCaP对辐射敏感（P = 0.04）。在异种移植有表达胰蛋白酶的PC 3细胞的小鼠中评价肿瘤生长和转移，所述小鼠每周接受5戈伊照射+/-A3.5 mg/kg AMD 3100每天腹膜内注射。与对照组相比，辐照的异种移植物显示出更高的CXCR 4（P = 0.006）和CXCL 12（P = 0.01）表达。治疗第4周时，AMD 3100使异种移植物对辐射敏感（P = 0.02）。然而，如生物发光成像所示，AMD 3100在第14天和第21天也动员了肿瘤细胞（P < 0.0001）。总之，AMD 3100可短暂增强前列腺癌的放射敏感性，但可诱导癌细胞动员。
Preclinical studies show that stroma affects sensitivity of prostate cancer cells via activation of the CXCR4/CXCL12 pathway. Here we studied the effect of CXCR4 inhibition combined with irradiation in prostate cancer cells. In an in vitro co-culture with stromal cells, the CXCR4 inhibitor AMD3100 sensitized prostate cancer cell lines PC3-Luc and LNCaP to irradiation (P = 0.04). Tumor growth and metastasis were evaluated in mice xenografted with luciferase-expressing PC3 cells that received 5 Gy irradiation weekly +/- A 3.5 mg/kg AMD3100 daily intraperitoneally. The irradiated xenografts showed higher CXCR4 (P = 0.006) and CXCL12 (P = 0.01) expression, compared to controls. AMD3100 sensitized the xenografts to irradiation at the fourth week of treatment (P = 0.02). However AMD3100 also mobilized tumor cells at days 14 and 21 (P < 0.0001), as shown by bioluminescent imaging. In conclusion, AMD3100 transiently enhances prostate cancer radiosensitivity, but induces cancer cell mobilization.