Author/Authors :
Lu، نويسنده , , Xin and Mu، نويسنده , , Euphemia and Wei، نويسنده , , Yong and Riethdorf، نويسنده , , Sabine and Yang، نويسنده , , Qifeng and Yuan، نويسنده , , Min and Yan، نويسنده , , Jun and Hua، نويسنده , , Yuling and Tiede، نويسنده , , Benjamin C.-Y. Lu، نويسنده , , Xuemin and Haffty، نويسنده , , Bruce G. and Pantel، نويسنده , , Klaus and Massagué، نويسنده , , Joan and Kang، نويسنده , , Yibin، نويسنده ,
Abstract :
Summary
cancer patients often develop locoregional or distant recurrence years after mastectomy. Understanding the mechanism of metastatic recurrence after dormancy is crucial for improving the cure rate for breast cancer. Here, we characterize a bone metastasis dormancy model to show that aberrant expression of vascular cell adhesion molecule 1 (VCAM-1), in part dependent on the activity of the NF-κB pathway, promotes the transition from indolent micrometastasis to overt metastasis. By interacting with the cognate receptor integrin α4β1, VCAM-1 recruits monocytic osteoclast progenitors and elevates local osteoclast activity. Antibodies against VCAM-1 and integrin α4 effectively inhibit bone metastasis progression and preserve bone structure. These findings establish VCAM-1 as a promising target for the prevention and inhibition of metastatic recurrence in bone.
