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*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

24 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 +/- 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.

Original languageEnglish
Pages (from-to)829-839
Number of pages11
JournalClinical & experimental metastasis
Volume31
Issue number7
DOIs
Publication statusPublished - Oct-2014

Keywords

  • CXCR4
  • AMD3100
  • Tumor cell mobilization
  • Radiosensitivity
  • BREAST-CANCER
  • DRUG-RESISTANCE
  • METASTASIS
  • EXPRESSION
  • GROWTH
  • MICROENVIRONMENT
  • ANTAGONIST
  • BONE
  • INFLAMMATION

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