| Literature DB >> 29232552 |
Hanqiu Zheng1, Yangjin Bae2, Sabine Kasimir-Bauer3, Rebecca Tang1, Jin Chen1, Guangwen Ren1, Min Yuan1, Mark Esposito1, Wenyang Li1, Yong Wei1, Minhong Shen1, Lanjing Zhang4, Nikolai Tupitsyn5, Klaus Pantel6, Chadwick King7, Jan Sun7, Jodi Moriguchi7, Helen Toni Jun8, Angela Coxon7, Brendan Lee9, Yibin Kang10.
Abstract
Bone metastasis is a major health threat to breast cancer patients. Tumor-derived Jagged1 represents a central node in mediating tumor-stromal interactions that promote osteolytic bone metastasis. Here, we report the development of a highly effective fully human monoclonal antibody against Jagged1 (clone 15D11). In addition to its inhibitory effect on bone metastasis of Jagged1-expressing tumor cells, 15D11 dramatically sensitizes bone metastasis to chemotherapy, which induces Jagged1 expression in osteoblasts to provide a survival niche for cancer cells. We further confirm the bone metastasis-promoting function of osteoblast-derived Jagged1 using osteoblast-specific Jagged1 transgenic mouse model. These findings establish 15D11 as a potential therapeutic agent for the prevention or treatment of bone metastasis.Entities:
Keywords: Jagged1; bone metastasis; breast cancer; chemoresistance; neutralizing antibody; osteoblastic niche; osteoblasts
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Year: 2017 PMID： 29232552 PMCID： PMC5729937 DOI： 10.1016/j.ccell.2017.11.002
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743