Method: For these studies, we employed the luciferase labeled human prostate cancer cell line (PC3). PC3 cells were inoculated into male SCID or Nude mice by intracardiac (i.c.) or intratibial (i.t.) injections, respectively following pretreatment with the antiresorptive agent, Zoledronic Acid (bisphosphonate (BP)) and/or AMD3100, which mobilizes hematopoietic stem cells (HSCs) out of the marrow making room for metastasis. Short term homing (24h) of PC-3 was assessed by QPCR for human Alu. Tumor growth was monitored by bioluminescent imaging. TRAP assays were used to determine the OC number.
Result: There were significant differences among the treatment groups prior to PCa injection; however, after PCa injection, the number of TRAP+ OCs was dramatically increased but did not differ significantly amongst the treatment groups. The pre and post BP treatments decreased the size of PCa lesions in the tibia, compared to the control.
Conclusion: The results indicate that OC activation is not necessary for PCa metastasis to bone at the most early stages, while clearing the marrow of HSCs (AMD3100) increased early PCa metastasis to bone. Together these findings suggest that the major role of OCs in metastasis are likely to support tumor growth rather than initial tumor seeding.