Cancer metastasis to the skeleton is a major problem with prostate cancer and requires the development of specialised approaches to treatment. Zoledronic acid, a bone resorptive agent, is currently the only bisphosphonate with proven benefit in prostate cancer. However, there is minimal research investigating whether Zoledronic acid modulates the early mechanisms involved in metastasis. The aim of this study is to determine whether different treatment regimes using Zoledronic acid modulate the early events in tumour/bone interactions.

Metatarsals from newborn mice (1-3 day old) are engrafted into a Dorsal Skinfold Chamber (DSC) implanted on a SCID mouse (5-6 weeks old). Prostate (PC3-GFP) cancer cells (1 × 105) are then injected via the heart (i.c) to simulate micrometastatic spread (n=20/group). Animals are treated with either i) weekly s.c injection of Zoledronic acid (25µg/kg/inection=100μg/kg in total) or saline or ii) single s.c injection of Zoledronic acid (100μg/kg) or saline for the 4 week study duration. The groups are further subdivided, so half of the animals receive treatment either before or after injection of tumour cells. Recordings of the chamber tissue and metatarsal are made at 48hr intervals for the duration of the experiment for the presence of PC3-GFP cells within the metatarsal. At the end of the study, tissue is harvested and processed for microCT, multi-photon analysis and histology.

TreatmentNumber of PC3-GFP cells homing to metatarsal
Day 3 Day 9 Day 15   
Weekly treatment before PC3-GFP cells 1.1 ± 0.1* 1.3 ± 0.2* 2.1 ± 0.3* 
Weekly treatment after PC3-GFP cells 3.2 ± 0.5* 3.4 ± 0.8* 4.4 ± 0.7* 
Single treatment before PC3-GFP cells 1.7 ± 0.3* 8.9 ± 0.9* 13.6 ± 0.8 
Control 3.2 ± 0.7 14.7 ± 1.0 15.9 ± 1.4 
TreatmentNumber of PC3-GFP cells homing to metatarsal
Day 3 Day 9 Day 15   
Weekly treatment before PC3-GFP cells 1.1 ± 0.1* 1.3 ± 0.2* 2.1 ± 0.3* 
Weekly treatment after PC3-GFP cells 3.2 ± 0.5* 3.4 ± 0.8* 4.4 ± 0.7* 
Single treatment before PC3-GFP cells 1.7 ± 0.3* 8.9 ± 0.9* 13.6 ± 0.8 
Control 3.2 ± 0.7 14.7 ± 1.0 15.9 ± 1.4 

Table 1. Number of PC3-GFP cells present in metatarsal after i.c. injection (*p<0.05 compared to control).

Treatment with Zoledronic acid reduces tumour cell homing to bone. Weekly treatment of Zoledronic acid prior to prostate cancer cell administration reduces homing to bone to a greater extent than the other treatment regimes test.

Funded by Sixth European Framework Programme (PROMET).

Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 470.