VCAM-1 Promotes Osteolytic Expansion of Indolent Bone Micrometastasis of Breast Cancer by Engaging α4β1-Positive Osteoclast Progenitors

Xin Lu, Euphemia Mu, Yong Wei, Sabine Riethdorf, Qifeng Yang, Min Yuan, Jun Yan, Yuling Hua, Benjamin J. Tiede, Xuemin Lu, Bruce G. Haffty, Klaus Pantel, Joan Massagué, Yibin Kang

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266 Scopus citations

Abstract

Breast 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.

Original languageEnglish (US)
Pages (from-to)701-714
Number of pages14
JournalCancer Cell
Volume20
Issue number6
DOIs
StatePublished - Dec 13 2011

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cell Biology
  • Cancer Research

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    Lu, X., Mu, E., Wei, Y., Riethdorf, S., Yang, Q., Yuan, M., Yan, J., Hua, Y., Tiede, B. J., Lu, X., Haffty, B. G., Pantel, K., Massagué, J., & Kang, Y. (2011). VCAM-1 Promotes Osteolytic Expansion of Indolent Bone Micrometastasis of Breast Cancer by Engaging α4β1-Positive Osteoclast Progenitors. Cancer Cell, 20(6), 701-714. https://doi.org/10.1016/j.ccr.2011.11.002