Metastatic recurrence of breast cancer years after successful treatment of the primary tumour is an important clinical problem, but the molecular events that control the activation of dormant micrometastases are poorly understood. Using a mouse model that recapitulates the transition from indolent micrometastases to overt bone metastasis, Lu et al. found that aberrant expression of vascular cell adhesion molecule 1 (VCAM1) in metastatic tumour cells recruits monocytic osteoclast progenitors through the VCAM1 receptor α4β1 integrin, thus increasing osteoclast activity and bone resorption. VCAM1 expression was partially dependent on activation of the nuclear factor-κB pathway. Furthermore, antibodies directed against VCAM1 or α4 integrin inhibited the progression of bone metastases in mice, and higher VCAM1 expression correlated with earlier relapse in patients with breast cancer. Therapeutically targeting this pathway may help to prevent metastatic recurrence of breast cancer.
ORIGINAL RESEARCH PAPER
Lu, X. et al. VCAM-1 promotes osteolytic expansion of indolent bone micrometastasis of breast cancer by engaging α4β1-positive osteoclast progenitors. Cancer Cell 30 Nov 2011 (doi:10.1016/j.ccr.2011.11.002)
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Seton-Rogers, S. Awakening a sleeping giant. Nat Rev Cancer 12, 6 (2012). https://doi.org/10.1038/nrc3200
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DOI: https://doi.org/10.1038/nrc3200