BoneKEy Reports | BoneKEy Watch

Cyclophosphamide promotes bone metastasis in prostate cancer



DOI:10.1038/bonekey.2012.138

Previous studies in various mouse models have shown that cyclophosphamide, a DNA-alkylating chemotherapy agent commonly used to treat non-Hodgkin's lymphoma, as well as breast and lung cancers, increases metastasis. In this study, Park et al. designed a series of experiments to investigate the impact of cyclophosphamide on metastasis from prostate cancer.

Mice primed with a single dose of cyclophosphamide, and unprimed controls, were injected 7 days later with luciferase-labeled cells from the prostate cancer PC-3 line, directly into the proximal tibiae. Primed mice showed a significantly greater incidence of hind limb metastases at days 7, 14 and 21. This observation seemed to be related to the change in bone marrow vascular integrity, and also to a temporary increase in serum cytokines and an expansion of myeloid lineage cells 7–10 days after cyclophosphamide treatment.

Particularly relevant to human therapeutics was a subsequent experiment, which showed that treating cyclophosphamide-primed mice with anti-CCL2 neutralizing antibodies in the 7 days between priming and injection of PC-3 cells prevented the observed increase in bone metastasis in primed mice.

Editor's comment: Cyclophosphamide, a bone-marrow suppressive chemotherapeutic drug, promotes prostate cancer skeletal outgrowth in mice. Although cyclophosphamide is not used in the treatment of advanced prostate cancer, careful attention should be paid to its use in the treatment of breast and lung cancers, where it is commonly included in chemotherapeutic regimens.


Creative Commons License This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 United States License.