Cancer Cell
Volume 20, Issue 6, 13 December 2011, Pages 701-714
Journal home page for Cancer Cell

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

https://doi.org/10.1016/j.ccr.2011.11.002Get rights and content
Under an Elsevier user license
open archive

Summary

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.

Highlights

► VCAM-1 expression is associated with early relapse and activation from dormancy ► VCAM-1 overexpression promotes bone metastasis by activating osteoclastogenesis ► VCAM-1-α4β1 binding facilitates adhesion of preosteoclasts to tumor cells ► VCAM-1 and α4 blocking antibodies reduce the progression of bone metastasis

Cited by (0)