| Literature DB >> 25154297 |
Urszula M Domanska1, Jennifer C Boer, Hetty Timmer-Bosscha, Marcel A T M van Vugt, Hilde D Hoving, Nathalie M Kliphuis, Stefano Rosati, Henk G van der Poel, Igle Jan de Jong, Elisabeth G E de Vries, Annemiek M E Walenkamp.
Abstract
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 ± 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.Entities:
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Year: 2014 PMID： 25154297 DOI： 10.1007/s10585-014-9673-2
Source DB: PubMed Journal: Clin Exp Metastasis ISSN： 0262-0898 Impact factor: 5.150