title: VCAM-1 promotes osteolytic expansion of indolent bone micrometastasis of breast cancer by engaging α4β1-positive osteoclast progenitors.
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.
authors.affiliation: Department of Molecular Biology, Princeton University, NJ 08544, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Lu
authors.forename: Euphemia
authors.initials: E
authors.lastname: Mu
authors.forename: Yong
authors.initials: Y
authors.lastname: Wei
authors.forename: Sabine
authors.initials: S
authors.lastname: Riethdorf
authors.forename: Qifeng
authors.initials: Q
authors.lastname: Yang
authors.forename: Min
authors.initials: M
authors.lastname: Yuan
authors.forename: Jun
authors.initials: J
authors.lastname: Yan
authors.forename: Yuling
authors.initials: Y
authors.lastname: Hua
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Tiede
authors.forename: Xuemin
authors.initials: X
authors.lastname: Lu
authors.forename: Bruce G
authors.initials: BG
authors.lastname: Haffty
authors.forename: Klaus
authors.initials: K
authors.lastname: Pantel
authors.forename: Joan
authors.initials: J
authors.lastname: Massagué
authors.forename: Yibin
authors.initials: Y
authors.lastname: Kang
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000378:metabolism / Q000517:prevention & control / Q000556:secondary*; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D002448:Cell Adhesion; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002633:Chemotaxis; D005260:Female; D006801:Humans; D039041:Integrin alpha4beta1 / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D058990:Molecular Targeted Therapy; D016328:NF-kappa B / Q000378:metabolism; D061206:Neoplasm Micrometastasis; D009368:Neoplasm Transplantation; D010010:Osteoclasts / Q000378:metabolism* / Q000473:pathology; D010014:Osteolysis / Q000000981:diagnostic imaging*; D011859:Radiography; D013234:Stem Cells / Q000378:metabolism* / Q000473:pathology; D014183:Transplantation, Heterologous; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D039041:Integrin alpha4beta1; D016328:NF-kappa B; D019010:Vascular Cell Adhesion Molecule-1