Therapeutic Antibody Targeting Tumor- and Osteoblastic Niche-Derived Jagged1 Sensitizes Bone Metastasis to Chemotherapy
| Autor: | Guangwen Ren, Chadwick T. King, Angela Coxon, Minhong Shen, Jodi Moriguchi, Mark Esposito, Jan Sun, Klaus Pantel, Yangjin Bae, Nikolai Tupitsyn, Min Yuan, Yibin Kang, Sabine Kasimir-Bauer, Helen Toni Jun, Yong Wei, Hanqiu Zheng, Rebecca Tang, Jin Chen, Brendan Lee, Lanjing Zhang, Wenyang Li |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Genetically modified mouse Cancer Research medicine.drug_class medicine.medical_treatment Medizin Clone (cell biology) Mice Transgenic Antineoplastic Agents Bone Neoplasms Monoclonal antibody Article Mice 03 medical and health sciences Breast cancer medicine Tumor Microenvironment Animals Humans Neutralizing antibody Chemotherapy Osteoblasts biology Receptors Notch business.industry Antibodies Monoclonal Bone metastasis medicine.disease Xenograft Model Antitumor Assays 030104 developmental biology Oncology Drug Resistance Neoplasm Cancer cell Cancer research biology.protein business Jagged-1 Protein |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|