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Journal of Orthopaedic Surgery and Research

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Open Access 01-12-2010 | Research article

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

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

Published in: Journal of Orthopaedic Surgery and Research | Issue 1/2010

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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Title: Role of the VEGF-Flt-1-FAK pathway in the pathogenesis of osteoclastic bone destruction of giant cell tumors of bone
Authors: Yoshihiro Matsumoto
Yuko Okada
Jun-ichi Fukushi
Satoshi Kamura
Toshifumi Fujiwara
Keiichiro Iida
Mihoko Koga
Shuichi Matsuda
Katsumi Harimaya
Akio Sakamoto
Yukihide Iwamoto
Publication date: 01-12-2010
Publisher: BioMed Central
Published in: Journal of Orthopaedic Surgery and Research / Issue 1/2010
Electronic ISSN: 1749-799X
DOI: https://doi.org/10.1186/1749-799X-5-85

At a glance: The STEP trials

Springer Medicine

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

Abstract

Background

Methods

Results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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