VCAM-1 promotes osteolytic expansion of indolent bone micrometastasis of breast cancer by engaging α4β1-positive osteoclast progenitors Journal Article
| Authors: | Lu, X.; Mu, E.; Wei, Y.; Riethdorf, S.; Yang, Q.; Yuan, M.; Yan, J.; Hua, Y.; Tiede, B. J.; Haffty, B. G.; Pantel, K.; Massague, J.; Kang, Y. |
| Article 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. © 2011 Elsevier Inc. |
| Keywords: | controlled study; human tissue; protein expression; bone neoplasms; osteolysis; nonhuman; bone metastasis; protein function; cell proliferation; mouse; animals; mice; cell function; breast cancer; vascular cell adhesion molecule 1; animal experiment; animal model; immunoglobulin enhancer binding protein; cell differentiation; cell line, tumor; breast neoplasms; mice, inbred balb c; antibodies, monoclonal; chemotaxis; mice, nude; nf-kappa b; micrometastasis; transplantation, heterologous; stem cells; osteoclast; osteoclasts; neoplasm transplantation; cell adhesion; vascular cell adhesion molecule-1; molecular targeted therapy; very late activation antigen 4; integrin alpha4beta1; neoplasm micrometastasis |
| Journal Title: | Cancer Cell |
| Volume: | 20 |
| Issue: | 6 |
| ISSN: | 1535-6108 |
| Publisher: | Cell Press |
| Date Published: | 2011-12-13 |
| Start Page: | 701 |
| End Page: | 714 |
| Language: | English |
| DOI: | 10.1016/j.ccr.2011.11.002 |
| PROVIDER: | scopus |
| PMCID: | PMC3241854 |
| PUBMED: | 22137794 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 1" - "Export Date: 3 January 2012" - "CODEN: CCAEC" - "Source: Scopus" |
