Skip to main content

Dissecting tumor-stromal interactions in breast cancer bone metastasis

Author(s): Kang, Y

To refer to this page use:
Full metadata record
DC FieldValueLanguage
dc.contributor.authorKang, Y-
dc.identifier.citationKang, Y. (2016). Dissecting tumor-stromal interactions in breast cancer bone metastasis. Endocrinology and Metabolism, 31 (2), 206 - 212. doi:10.3803/EnM.2016.31.2.206en_US
dc.description.abstractBone metastasis is a frequent occurrence in breast cancer, affecting more than 70% of late stage cancer patients with severe complications such as fracture, bone pain, and hypercalcemia. The pathogenesis of osteolytic bone metastasis depends on cross-communications between tumor cells and various stromal cells residing in the bone micro environment. Several growth factor signaling pathways, secreted micro RNAs (miRNAs) and exosomes are functional mediators of tumor-stromal interactions in bone metastasis.We developed a functional genomic approach to systemically identified molecular pathways utilized by breast cancer cells to engage the bone stroma in order to generate osteolytic bone metastasis. We showed that elevated expression of vascularcell adhesion molecule 1 (VCAM1) in disseminated breast tumor cells mediates the recruitment of pre-osteoclasts and promotestheir differentiation to mature osteoclasts during the bone metastasis formation. Transforming growth factor β (TGF-β) is releasedfrom bone matrix upon bone destruction, and signals to breast cancer to further enhance their malignancy in developing bone metastasis.We furthered identified Jagged1 as a TGF-β target genes in tumor cells that engaged bone stromal cells through the activation of Notch signaling to provide a positive feedback to promote tumor growth and to activate osteoclast differentiation. Substantially change in miRNA expression was observed in osteoclasts during their differentiation and maturation, which can be exploitedas circulating biomarkers of emerging bone metastasis and therapeutic targets for the treatment of bone metastasis. Further research in this direction may lead to improved diagnosis and treatment strategies for bone metastasis.en_US
dc.format.extent1 - 7en_US
dc.relation.ispartofEndocrinology and Metabolismen_US
dc.rightsFinal published version. Article is made available in OAR by the publisher's permission or policy.en_US
dc.titleDissecting tumor-stromal interactions in breast cancer bone metastasisen_US
dc.typeJournal Articleen_US

Files in This Item:
File Description SizeFormat 
Dissecting Tumor-Stromal Interactions in Breast Cancer.pdf1.2 MBAdobe PDFView/Download

Items in OAR@Princeton are protected by copyright, with all rights reserved, unless otherwise indicated.