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Disruption of CXCR4 enhances osteoclastogenesis and tumor growth in bone

by Hirbe, Angela C , Morgan, Elizabeth A , Piwnica-Worms, David , Rubin, Jessica , Uluçkan, Özge , Eagleton, Mark C , Prior, Julie L , Weilbaecher, Katherine N

in Animal traps / Animals / Biological Sciences / Bone Density Conservation Agents - therapeutic use / Bone Neoplasms - genetics / Bone Neoplasms - pathology / Bone Resorption / Bones / Cancer / Cell Division / Cell growth / CXCR4 receptor / Diphosphonates - therapeutic use / hematopoietic stem cells / Imidazoles - therapeutic use / Kinetics / Liver cells / Macrophages / Macrophages - pathology / Macrophages - physiology / metastasis / Mice / Mice, Knockout / neoplasm cells / Neoplasm Metastasis / Oncology / osteoclasts / Osteoclasts - pathology / Receptors, CXCR4 - deficiency / Receptors, CXCR4 - genetics / Rodents / Stromal cells / T lymphocytes / Tumor burden / Tumors / Zoledronic Acid

2007

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Disruption of CXCR4 enhances osteoclastogenesis and tumor growth in bone

by Hirbe, Angela C , Morgan, Elizabeth A , Piwnica-Worms, David , Rubin, Jessica , Uluçkan, Özge , Eagleton, Mark C , Prior, Julie L , Weilbaecher, Katherine N

2007

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Disruption of CXCR4 enhances osteoclastogenesis and tumor growth in bone

by Hirbe, Angela C , Morgan, Elizabeth A , Piwnica-Worms, David , Rubin, Jessica , Uluçkan, Özge , Eagleton, Mark C , Prior, Julie L , Weilbaecher, Katherine N

2007

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Journal Article

Disruption of CXCR4 enhances osteoclastogenesis and tumor growth in bone

Hirbe, Angela C,

Morgan, Elizabeth A,

Piwnica-Worms, David,

Rubin, Jessica,

Uluçkan, Özge,

Eagleton, Mark C,

Prior, Julie L,

Weilbaecher, Katherine N

2007

Overview

CXCR4 regulates hematopoietic and tumor cell homing to bone, but its role during osteoclast (OC) development is unknown. We investigated the role of CXCR4 in osteoclastogenesis and in a model of bone metastasis. Compared with controls, mice reconstituted with CXCR4 null hematopoietic cells exhibited elevated markers of bone resorption, increased OC perimeter along bone, and increased bone loss. CXCR4-/- OCs demonstrated accelerated differentiation and enhanced bone resorption in vitro. Furthermore, tumor growth specifically in bone was significantly increased in mice reconstituted with CXCR4-/- hematopoietic cells. Finally, enhancement of bone tumor growth in the absence of CXCR4 was abrogated with the OC inhibitor, zoledronic acid. These data demonstrate that disruption of CXCR4 enhances osteoclastogenesis and suggest that inhibition of CXCR4 may enhance established skeletal tumor burden by increasing OC activity.

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Publisher

National Academy of Sciences,National Acad Sciences

Subject

Animal traps

/ Animals

/ Biological Sciences

/ Bone Density Conservation Agents - therapeutic use

/ Bone Neoplasms - genetics

/ Bone Neoplasms - pathology

/ Bone Resorption