Format

Send to

Choose Destination
Cancer Cell. 2011 Feb 15;19(2):192-205. doi: 10.1016/j.ccr.2010.12.022. Epub 2011 Feb 3.

Tumor-derived JAGGED1 promotes osteolytic bone metastasis of breast cancer by engaging notch signaling in bone cells.

Author information

1
Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.

Abstract

Despite evidence supporting an oncogenic role in breast cancer, the Notch pathway's contribution to metastasis remains unknown. Here, we report that the Notch ligand Jagged1 is a clinically and functionally important mediator of bone metastasis by activating the Notch pathway in bone cells. Jagged1 promotes tumor growth by stimulating IL-6 release from osteoblasts and directly activates osteoclast differentiation. Furthermore, Jagged1 is a potent downstream mediator of the bone metastasis cytokine TGFβ that is released during bone destruction. Importantly, γ-secretase inhibitor treatment reduces Jagged1-mediated bone metastasis by disrupting the Notch pathway in stromal bone cells. These findings elucidate a stroma-dependent mechanism for Notch signaling in breast cancer and provide rationale for using γ-secretase inhibitors for the treatment of bone metastasis.

PMID:
21295524
PMCID:
PMC3040415
DOI:
10.1016/j.ccr.2010.12.022
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center