TY - JOUR
T1 - CXCR4 inhibition enhances radiosensitivity, while inducing cancer cell mobilization in a prostate cancer mouse model
AU - Domanska, Urszula M.
AU - Boer, Jennifer C.
AU - Timmer-Bosscha, Hetty
AU - van Vugt, Marcel A.T.M.
AU - Hoving, Hilde D.
AU - Kliphuis, Nathalie M.
AU - Rosati, Stefano
AU - van der Poel, Henk G.
AU - de Jong, Igle Jan
AU - de Vries, Elisabeth G.E.
AU - Walenkamp, Annemiek M.E.
PY - 2014/10
Y1 - 2014/10
N2 - 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.
AB - 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.
KW - AMD3100
KW - CXCR4
KW - Radiosensitivity
KW - Tumor cell mobilization
UR - http://www.scopus.com/inward/record.url?scp=84910135124&partnerID=8YFLogxK
U2 - 10.1007/s10585-014-9673-2
DO - 10.1007/s10585-014-9673-2
M3 - Article
C2 - 25154297
AN - SCOPUS:84910135124
SN - 0262-0898
VL - 31
SP - 829
EP - 839
JO - Clinical and Experimental Metastasis
JF - Clinical and Experimental Metastasis
IS - 7
ER -
