Therapeutic Antibody Targeting Tumor- and Osteoblastic Niche-Derived Jagged1 Sensitizes Bone Metastasis to Chemotherapy
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Therapeutic Antibody Targeting Tumor- and Osteoblastic Niche-Derived Jagged1 Sensitizes Bone Metastasis to Chemotherapy. / Zheng, Hanqiu; Bae, Yangjin; Kasimir-Bauer, Sabine; Tang, Rebecca; Chen, Jin; Ren, Guangwen; Yuan, Min; Esposito, Mark; Li, Wenyang; Wei, Yong; Shen, Minhong; Zhang, Lanjing; Tupitsyn, Nikolai; Pantel, Klaus; King, Chadwick; Sun, Jan; Moriguchi, Jodi; Jun, Helen Toni; Coxon, Angela; Lee, Brendan; Kang, Yibin.
in: CANCER CELL, Jahrgang 32, Nr. 6, 11.12.2017, S. 731-747.e6.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Therapeutic Antibody Targeting Tumor- and Osteoblastic Niche-Derived Jagged1 Sensitizes Bone Metastasis to Chemotherapy
AU - Zheng, Hanqiu
AU - Bae, Yangjin
AU - Kasimir-Bauer, Sabine
AU - Tang, Rebecca
AU - Chen, Jin
AU - Ren, Guangwen
AU - Yuan, Min
AU - Esposito, Mark
AU - Li, Wenyang
AU - Wei, Yong
AU - Shen, Minhong
AU - Zhang, Lanjing
AU - Tupitsyn, Nikolai
AU - Pantel, Klaus
AU - King, Chadwick
AU - Sun, Jan
AU - Moriguchi, Jodi
AU - Jun, Helen Toni
AU - Coxon, Angela
AU - Lee, Brendan
AU - Kang, Yibin
N1 - Copyright © 2017 Elsevier Inc. All rights reserved.
PY - 2017/12/11
Y1 - 2017/12/11
N2 - 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.
AB - 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.
KW - Animals
KW - Antibodies, Monoclonal
KW - Antineoplastic Agents
KW - Bone Neoplasms
KW - Humans
KW - Jagged-1 Protein
KW - Mice
KW - Mice, Transgenic
KW - Osteoblasts
KW - Xenograft Model Antitumor Assays
KW - Journal Article
U2 - 10.1016/j.ccell.2017.11.002
DO - 10.1016/j.ccell.2017.11.002
M3 - SCORING: Journal article
C2 - 29232552
VL - 32
SP - 731-747.e6
JO - CANCER CELL
JF - CANCER CELL
SN - 1535-6108
IS - 6
ER -