title: CXCR4 inhibition enhances radiosensitivity, while inducing cancer cell mobilization in a prostate cancer mouse model.
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.
authors.affiliation: Departments of Medical Oncology, University Medical Center Groningen, University of Groningen, P.O. Box 30.00, 19700 RB, Groningen, The Netherlands.
authors.forename: Urszula M
authors.initials: UM
authors.lastname: Domanska
authors.forename: Jennifer C
authors.initials: JC
authors.lastname: Boer
authors.forename: Hetty
authors.initials: H
authors.lastname: Timmer-Bosscha
authors.forename: Marcel A T M
authors.initials: MA
authors.lastname: van Vugt
authors.forename: Hilde D
authors.initials: HD
authors.lastname: Hoving
authors.forename: Nathalie M
authors.initials: NM
authors.lastname: Kliphuis
authors.forename: Stefano
authors.initials: S
authors.lastname: Rosati
authors.forename: Henk G
authors.initials: HG
authors.lastname: van der Poel
authors.forename: Igle Jan
authors.initials: IJ
authors.lastname: de Jong
authors.forename: Elisabeth G E
authors.initials: EG
authors.lastname: de Vries
authors.forename: Annemiek M E
authors.initials: AM
authors.lastname: Walenkamp
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D011471:Prostatic Neoplasms / Q000473:pathology*; D011836:Radiation Tolerance; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors* / Q000502:physiology
chemical_list: C514936:CXCR4 protein, mouse; D019718:Receptors, CXCR4