VCAM-1 Promotes Osteolytic Expansion of Indolent Bone Micrometastasis of Breast Cancer by Engaging ±4²1-Positive Osteoclast Progenitors
Menée à l'aide de xénogreffes, cette étude montre que la surexpression de la molécule d'adhérence cellulaire vasculaire VCAM-1 favorise la transformation d'une micrométastase indolente en métastase avérée dans le cancer du sein
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-ºB pathway, promotes the transition from indolent micrometastasis to overt metastasis. By interacting with the cognate receptor integrin ±4²1, VCAM-1 recruits monocytic osteoclast progenitors and elevates local osteoclast activity. Antibodies against VCAM-1 and integrin ±4 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. º VCAM-1 expression is associated with early relapse and activation from dormancy º VCAM-1 overexpression promotes bone metastasis by activating osteoclastogenesis º VCAM-1-±4²1 binding facilitates adhesion of preosteoclasts to tumor cells º VCAM-1 and ±4 blocking antibodies reduce the progression of bone metastasis