The bone destruction attending skeletal metastasis is mediated by tumor-recruited osteoclasts (OCs). Hence, OCs are principal therapeutic targets in afflicted individuals. On the other hand, one-third of patients develop further skeletal-related events within two years of initiating antiresorptive therapies, suggesting that additional cells modulate bone tumor growth. Previous studies showing amelioration of bone metastases by targeting the OCs were performed in immune-compromised animals injected with human breast cancer cells. Consequently, the contribution of the immune system to bone tumor growth was unclear. Using genetic models of immune and OC modulation (PLCγ2 andLyn), as well as pharmacological inhibition of OCs and T cells, we now demonstrate that a condition of immune deficiency can interfere with the antitumor effects of OC blockade. Thus, our findings expand the current tumor/bone vicious cycle model to include T cells as additional regulators of bone tumor growth, regardless of the OC status.

Original languageEnglish
Pages (from-to)71-78
Number of pages8
JournalAnnals of the New York Academy of Sciences
Issue number1
StatePublished - Nov 2011


  • Bone metastases
  • Cancer
  • Osteoclasts
  • T cells
  • Vicious cycle


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