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IL-11 is essential in promoting osteolysis in breast cancer bone metastasis via RANKL-independent activation of osteoclastogenesis
by
Gong, Xiaoshan
, Ma, Qinyu
, Dai, Qijie
, Dong, Rui
, Dong, Shiwu
, Ding, Ning
, Bai, Yun
, Dou, Ce
, Luo, Fei
, Liang, Mengmeng
, Kang, Fei
, Dai, Jingjin
in
13
/ 13/21
/ 13/51
/ 14
/ 14/5
/ 38
/ 38/77
/ 59
/ 631/80/304
/ 631/80/86/2364
/ 64/60
/ 82/1
/ Animals
/ Antibodies
/ Biochemistry
/ Biomedical and Life Sciences
/ Bone and Bones - diagnostic imaging
/ Bone and Bones - pathology
/ Bone cancer
/ Bone growth
/ Bone Neoplasms - mortality
/ Bone Neoplasms - pathology
/ Bone Neoplasms - secondary
/ Breast cancer
/ Breast Neoplasms - pathology
/ c-Myc protein
/ Cell Biology
/ Cell Culture
/ Cell Line, Tumor
/ Female
/ Humans
/ Immunology
/ Interleukin 11
/ Interleukin-11 - metabolism
/ Interleukin-11 - pharmacology
/ Interleukin-11 - therapeutic use
/ Janus kinase
/ Janus Kinase 1 - metabolism
/ Kaplan-Meier Estimate
/ Life Sciences
/ Macrophage Colony-Stimulating Factor - pharmacology
/ Macrophage Colony-Stimulating Factor - therapeutic use
/ Metastases
/ Metastasis
/ Mice
/ Mice, Inbred BALB C
/ Mice, Nude
/ Myc protein
/ Osteoclastogenesis
/ Osteogenesis - drug effects
/ Osteolysis
/ Osteolysis - pathology
/ Osteolysis - prevention & control
/ Phosphorylation
/ RANK Ligand - pharmacology
/ RANK Ligand - therapeutic use
/ Signal transduction
/ Signal Transduction - drug effects
/ Stat3 protein
/ STAT3 Transcription Factor - metabolism
/ TRANCE protein
/ Tyrphostins - pharmacology
/ Tyrphostins - therapeutic use
2019
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IL-11 is essential in promoting osteolysis in breast cancer bone metastasis via RANKL-independent activation of osteoclastogenesis
by
Gong, Xiaoshan
, Ma, Qinyu
, Dai, Qijie
, Dong, Rui
, Dong, Shiwu
, Ding, Ning
, Bai, Yun
, Dou, Ce
, Luo, Fei
, Liang, Mengmeng
, Kang, Fei
, Dai, Jingjin
in
13
/ 13/21
/ 13/51
/ 14
/ 14/5
/ 38
/ 38/77
/ 59
/ 631/80/304
/ 631/80/86/2364
/ 64/60
/ 82/1
/ Animals
/ Antibodies
/ Biochemistry
/ Biomedical and Life Sciences
/ Bone and Bones - diagnostic imaging
/ Bone and Bones - pathology
/ Bone cancer
/ Bone growth
/ Bone Neoplasms - mortality
/ Bone Neoplasms - pathology
/ Bone Neoplasms - secondary
/ Breast cancer
/ Breast Neoplasms - pathology
/ c-Myc protein
/ Cell Biology
/ Cell Culture
/ Cell Line, Tumor
/ Female
/ Humans
/ Immunology
/ Interleukin 11
/ Interleukin-11 - metabolism
/ Interleukin-11 - pharmacology
/ Interleukin-11 - therapeutic use
/ Janus kinase
/ Janus Kinase 1 - metabolism
/ Kaplan-Meier Estimate
/ Life Sciences
/ Macrophage Colony-Stimulating Factor - pharmacology
/ Macrophage Colony-Stimulating Factor - therapeutic use
/ Metastases
/ Metastasis
/ Mice
/ Mice, Inbred BALB C
/ Mice, Nude
/ Myc protein
/ Osteoclastogenesis
/ Osteogenesis - drug effects
/ Osteolysis
/ Osteolysis - pathology
/ Osteolysis - prevention & control
/ Phosphorylation
/ RANK Ligand - pharmacology
/ RANK Ligand - therapeutic use
/ Signal transduction
/ Signal Transduction - drug effects
/ Stat3 protein
/ STAT3 Transcription Factor - metabolism
/ TRANCE protein
/ Tyrphostins - pharmacology
/ Tyrphostins - therapeutic use
2019
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IL-11 is essential in promoting osteolysis in breast cancer bone metastasis via RANKL-independent activation of osteoclastogenesis
by
Gong, Xiaoshan
, Ma, Qinyu
, Dai, Qijie
, Dong, Rui
, Dong, Shiwu
, Ding, Ning
, Bai, Yun
, Dou, Ce
, Luo, Fei
, Liang, Mengmeng
, Kang, Fei
, Dai, Jingjin
in
13
/ 13/21
/ 13/51
/ 14
/ 14/5
/ 38
/ 38/77
/ 59
/ 631/80/304
/ 631/80/86/2364
/ 64/60
/ 82/1
/ Animals
/ Antibodies
/ Biochemistry
/ Biomedical and Life Sciences
/ Bone and Bones - diagnostic imaging
/ Bone and Bones - pathology
/ Bone cancer
/ Bone growth
/ Bone Neoplasms - mortality
/ Bone Neoplasms - pathology
/ Bone Neoplasms - secondary
/ Breast cancer
/ Breast Neoplasms - pathology
/ c-Myc protein
/ Cell Biology
/ Cell Culture
/ Cell Line, Tumor
/ Female
/ Humans
/ Immunology
/ Interleukin 11
/ Interleukin-11 - metabolism
/ Interleukin-11 - pharmacology
/ Interleukin-11 - therapeutic use
/ Janus kinase
/ Janus Kinase 1 - metabolism
/ Kaplan-Meier Estimate
/ Life Sciences
/ Macrophage Colony-Stimulating Factor - pharmacology
/ Macrophage Colony-Stimulating Factor - therapeutic use
/ Metastases
/ Metastasis
/ Mice
/ Mice, Inbred BALB C
/ Mice, Nude
/ Myc protein
/ Osteoclastogenesis
/ Osteogenesis - drug effects
/ Osteolysis
/ Osteolysis - pathology
/ Osteolysis - prevention & control
/ Phosphorylation
/ RANK Ligand - pharmacology
/ RANK Ligand - therapeutic use
/ Signal transduction
/ Signal Transduction - drug effects
/ Stat3 protein
/ STAT3 Transcription Factor - metabolism
/ TRANCE protein
/ Tyrphostins - pharmacology
/ Tyrphostins - therapeutic use
2019
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IL-11 is essential in promoting osteolysis in breast cancer bone metastasis via RANKL-independent activation of osteoclastogenesis
Journal Article
IL-11 is essential in promoting osteolysis in breast cancer bone metastasis via RANKL-independent activation of osteoclastogenesis
2019
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Overview
A variety of osteolytic factors have been identified from breast cancer cells leading to osteolysis, but less is known about which factor plays an essential role in the initiation process prior to the overt vicious osteolytic cycle. Here, we present in vitro and in vivo evidences to clarify the role of interleukin-11 (IL-11) as an essential contributor to breast cancer bone metastasis mediated osteolysis. Animal studies showed that bone specific metastatic BoM-1833 cells induce earlier onset of osteolysis and faster tumor growth compared with MCF7 and parental MDA-MB-231 cells in BALB/c-nu/nu nude mice. IL-11 was further screened and identified as the indispensable factor secreted by BoM-1833 cells inducing osteoclastogenesis independently of receptor activator of nuclear factor κB ligand (RANKL). Mechanistic investigation revealed that the JAK1/STAT3 signaling pathway as a downstream effector of IL-11, STAT3 activation further induces the expression of c-Myc, a necessary factor required for osteoclastogenesis. By inhibiting STAT3 phosphorylation, AG-490 was shown effective in reducing osteolysis and tumor growth in the metastatic niche. Overall, our results revealed the essential role and the underlying molecular mechanism of IL-11 in breast cancer bone metastasis mediated osteolysis. STAT3 targeting through AG-490 is a potential therapeutic strategy for mitigating osteolysis and tumor growth of bone metastatic breast cancer.
Publisher
Nature Publishing Group UK,Springer Nature B.V
Subject
/ 13/21
/ 13/51
/ 14
/ 14/5
/ 38
/ 38/77
/ 59
/ 64/60
/ 82/1
/ Animals
/ Biomedical and Life Sciences
/ Bone and Bones - diagnostic imaging
/ Breast Neoplasms - pathology
/ Female
/ Humans
/ Interleukin-11 - pharmacology
/ Interleukin-11 - therapeutic use
/ Macrophage Colony-Stimulating Factor - pharmacology
/ Macrophage Colony-Stimulating Factor - therapeutic use
/ Mice
/ Osteolysis - prevention & control
/ RANK Ligand - therapeutic use
/ Signal Transduction - drug effects
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