Role of the VEGF-Flt-1-FAK pathway in the pathogenesis of osteoclastic bone destruction of giant cell tumors of bone

Yoshihiro Matsumoto, Yuko Okada, Jun ichi Fukushi, Satoshi Kamura, Toshifumi Fujiwara, Keiichiro Iida, Mihoko Koga, Shuichi Matsuda, Katsumi Harimaya, Akio Sakamoto, Yukihide Iwamoto

Research output: Contribution to journalArticle

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Abstract

Background: Giant cell tumors (GCTs) of bone are primary benign bone tumors that are characterized by a high number of osteoclast-like multinuclear giant cells (MNCs). Recent studies suggest that the spindle-shaped stromal cells in GCTs are tumor cells, while monocyte-like cells and MNCs are reactive osteoclast precursor cells (OPCs) and osteoclasts (OCs), respectively. In this study, we investigated the pathogenesis of osteoclastic bone destruction in GCTs by focusing on the role of the vascular endothelial growth factor (VEGF)-Flt-1 (type-1 VEGF receptor)-focal adhesion kinase (FAK) pathway.Methods: The motility of OPCs cells was assessed by a chemotaxis assay and the growth of OPCs was examined using a cell proliferation assay. The expression of VEGF and activation of Flt-1 and FAK in clinical GCT samples and in OPCs were detected by immunohistochemistry and immunoblotting. The correlation between the expression levels of activated Flt-1 and FAK and clinical stages of GCTs was investigated by immunohistochemistry.Results: In GCT samples, CD68, a marker of OPCs and OCs, co-localized with Flt-1. Conditioned media from GCT tissue (GCT-CM) enhanced the chemotaxis and proliferation of OPCs. GCT-CM also stimulated FAK activation in OPCs in vitro. Moreover, there was a correlation between the clinical stage of GCTs and the expression of tyrosine-phosphorylated Flt-1 and FAK.Conclusions: Our results suggest that the VEGF-Flt-1-FAK pathway is involved in the pathogenesis of bone destruction of GCTs.

Original languageEnglish
Article number85
JournalJournal of Orthopaedic Surgery and Research
Volume5
Issue number1
DOIs
Publication statusPublished - Nov 9 2010

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Focal Adhesion Kinase 1
Giant Cell Tumor of Bone
Giant Cell Tumors
Osteoclasts
Vascular Endothelial Growth Factor A
Bone and Bones
Focal Adhesion Protein-Tyrosine Kinases
Chemotaxis
Giant Cells
Immunohistochemistry
Vascular Endothelial Growth Factor Receptor-1
Stromal Cells
Conditioned Culture Medium
Immunoblotting

All Science Journal Classification (ASJC) codes

  • Surgery
  • Orthopedics and Sports Medicine

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Role of the VEGF-Flt-1-FAK pathway in the pathogenesis of osteoclastic bone destruction of giant cell tumors of bone. / Matsumoto, Yoshihiro; Okada, Yuko; Fukushi, Jun ichi; Kamura, Satoshi; Fujiwara, Toshifumi; Iida, Keiichiro; Koga, Mihoko; Matsuda, Shuichi; Harimaya, Katsumi; Sakamoto, Akio; Iwamoto, Yukihide.

In: Journal of Orthopaedic Surgery and Research, Vol. 5, No. 1, 85, 09.11.2010.

Research output: Contribution to journalArticle

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abstract = "Background: Giant cell tumors (GCTs) of bone are primary benign bone tumors that are characterized by a high number of osteoclast-like multinuclear giant cells (MNCs). Recent studies suggest that the spindle-shaped stromal cells in GCTs are tumor cells, while monocyte-like cells and MNCs are reactive osteoclast precursor cells (OPCs) and osteoclasts (OCs), respectively. In this study, we investigated the pathogenesis of osteoclastic bone destruction in GCTs by focusing on the role of the vascular endothelial growth factor (VEGF)-Flt-1 (type-1 VEGF receptor)-focal adhesion kinase (FAK) pathway.Methods: The motility of OPCs cells was assessed by a chemotaxis assay and the growth of OPCs was examined using a cell proliferation assay. The expression of VEGF and activation of Flt-1 and FAK in clinical GCT samples and in OPCs were detected by immunohistochemistry and immunoblotting. The correlation between the expression levels of activated Flt-1 and FAK and clinical stages of GCTs was investigated by immunohistochemistry.Results: In GCT samples, CD68, a marker of OPCs and OCs, co-localized with Flt-1. Conditioned media from GCT tissue (GCT-CM) enhanced the chemotaxis and proliferation of OPCs. GCT-CM also stimulated FAK activation in OPCs in vitro. Moreover, there was a correlation between the clinical stage of GCTs and the expression of tyrosine-phosphorylated Flt-1 and FAK.Conclusions: Our results suggest that the VEGF-Flt-1-FAK pathway is involved in the pathogenesis of bone destruction of GCTs.",
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T1 - Role of the VEGF-Flt-1-FAK pathway in the pathogenesis of osteoclastic bone destruction of giant cell tumors of bone

AU - Matsumoto, Yoshihiro

AU - Okada, Yuko

AU - Fukushi, Jun ichi

AU - Kamura, Satoshi

AU - Fujiwara, Toshifumi

AU - Iida, Keiichiro

AU - Koga, Mihoko

AU - Matsuda, Shuichi

AU - Harimaya, Katsumi

AU - Sakamoto, Akio

AU - Iwamoto, Yukihide

PY - 2010/11/9

Y1 - 2010/11/9

N2 - Background: Giant cell tumors (GCTs) of bone are primary benign bone tumors that are characterized by a high number of osteoclast-like multinuclear giant cells (MNCs). Recent studies suggest that the spindle-shaped stromal cells in GCTs are tumor cells, while monocyte-like cells and MNCs are reactive osteoclast precursor cells (OPCs) and osteoclasts (OCs), respectively. In this study, we investigated the pathogenesis of osteoclastic bone destruction in GCTs by focusing on the role of the vascular endothelial growth factor (VEGF)-Flt-1 (type-1 VEGF receptor)-focal adhesion kinase (FAK) pathway.Methods: The motility of OPCs cells was assessed by a chemotaxis assay and the growth of OPCs was examined using a cell proliferation assay. The expression of VEGF and activation of Flt-1 and FAK in clinical GCT samples and in OPCs were detected by immunohistochemistry and immunoblotting. The correlation between the expression levels of activated Flt-1 and FAK and clinical stages of GCTs was investigated by immunohistochemistry.Results: In GCT samples, CD68, a marker of OPCs and OCs, co-localized with Flt-1. Conditioned media from GCT tissue (GCT-CM) enhanced the chemotaxis and proliferation of OPCs. GCT-CM also stimulated FAK activation in OPCs in vitro. Moreover, there was a correlation between the clinical stage of GCTs and the expression of tyrosine-phosphorylated Flt-1 and FAK.Conclusions: Our results suggest that the VEGF-Flt-1-FAK pathway is involved in the pathogenesis of bone destruction of GCTs.

AB - Background: Giant cell tumors (GCTs) of bone are primary benign bone tumors that are characterized by a high number of osteoclast-like multinuclear giant cells (MNCs). Recent studies suggest that the spindle-shaped stromal cells in GCTs are tumor cells, while monocyte-like cells and MNCs are reactive osteoclast precursor cells (OPCs) and osteoclasts (OCs), respectively. In this study, we investigated the pathogenesis of osteoclastic bone destruction in GCTs by focusing on the role of the vascular endothelial growth factor (VEGF)-Flt-1 (type-1 VEGF receptor)-focal adhesion kinase (FAK) pathway.Methods: The motility of OPCs cells was assessed by a chemotaxis assay and the growth of OPCs was examined using a cell proliferation assay. The expression of VEGF and activation of Flt-1 and FAK in clinical GCT samples and in OPCs were detected by immunohistochemistry and immunoblotting. The correlation between the expression levels of activated Flt-1 and FAK and clinical stages of GCTs was investigated by immunohistochemistry.Results: In GCT samples, CD68, a marker of OPCs and OCs, co-localized with Flt-1. Conditioned media from GCT tissue (GCT-CM) enhanced the chemotaxis and proliferation of OPCs. GCT-CM also stimulated FAK activation in OPCs in vitro. Moreover, there was a correlation between the clinical stage of GCTs and the expression of tyrosine-phosphorylated Flt-1 and FAK.Conclusions: Our results suggest that the VEGF-Flt-1-FAK pathway is involved in the pathogenesis of bone destruction of GCTs.

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