CXCR4 inhibition enhances radiosensitivity, while inducing cancer cell mobilization in a prostate cancer mouse model

Urszula M. Domanska, 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

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20 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)829-839
Number of pages11
JournalClinical and Experimental Metastasis
Volume31
Issue number7
DOIs
Publication statusPublished - Oct 2014
Externally publishedYes

Keywords

  • AMD3100
  • CXCR4
  • Radiosensitivity
  • Tumor cell mobilization

Cite this

Domanska, U. M., Boer, J. C., Timmer-Bosscha, H., van Vugt, M. A. T. M., Hoving, H. D., Kliphuis, N. M., Rosati, S., van der Poel, H. G., de Jong, I. J., de Vries, E. G. E., & Walenkamp, A. M. E. (2014). CXCR4 inhibition enhances radiosensitivity, while inducing cancer cell mobilization in a prostate cancer mouse model. Clinical and Experimental Metastasis, 31(7), 829-839. https://doi.org/10.1007/s10585-014-9673-2