BoneKEy Reports | BoneKEy Watch
Mechanism that underlies expansion of distant bone metastases
DOI:10.1038/bonekey.2012.21
It has long been a mystery why women apparently cured of a primary breast tumor experience distant relapse after many years of disease-free survival. Lu et al. have now developed a mouse model to enhance our understanding of the molecular basis of metastatic dormancy.
They show that cells that represent indolent micrometastases in bone marrow may express vascular cell adhesion molecule 1 (VCAM-1), which recruits osteoclast progenitor cells in the bone marrow via the cognate receptor integrin α4β1. Osteoclast activity in the local environment is then increased, converting the micrometastases into overt metastatic tumors.
The potential therapeutic applications of the findings from the mouse model are highlighted; antibodies against VCAM-1 and integrin α4β1 were able to inhibit the progression to metastasis and preserved the normal structure of the bone. VCAM-1 could therefore represent a potential target for preventing and treating late bone metastases in women who have had breast cancer.
Editor's comment: Understanding mechanisms of tumor dormancy and their reactivation have important clinical implications for controlling metastatic progression. Vascular cell adhesion molecule 1 (VCAM-1) expression in breast cancer cells has been identified as a key regulator that promotes the switch from dormant micrometastasis to overt metastasis.
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