Vascular endothelial growth factor acts as an osteolytic factor in breast cancer metastases to bone

• Published in: British journal of cancer Vol. 92; no. 8; pp. 1531 - 1537
• Main Authors: ALDRIDGE, S. E, LENNARD, T. W. J, WILLIAMS, J. R, BIRCH, M. A
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 25.04.2005
• Subjects: Adult; Aged; Animals; Biological and medical sciences; Bone Neoplasms - metabolism; Bone Neoplasms - secondary; Breast cancer; Breast Neoplasms - pathology; Cancer research; Carrier Proteins - pharmacology; Cell Differentiation - drug effects; Cells, Cultured - drug effects; Cells, Cultured - metabolism; Humans; Immunohistochemistry; Medical research; Medical sciences; Membrane Glycoproteins - pharmacology; Metastasis; Middle Aged; Molecular Diagnostics; Monocytes - drug effects; Monocytes - metabolism; Osteoclasts - cytology; Osteoclasts - drug effects; Osteoclasts - metabolism; Osteolysis - metabolism; RANK Ligand; Receptor Activator of Nuclear Factor-kappa B; Receptors, Vascular Endothelial Growth Factor; Tumors; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - metabolism; Vascular Endothelial Growth Factor A - pharmacology; VEGFR2; VEGF; Uncooked food; Osteoclast; Breast cancer; RAW 264.7; Metastasis; Malignant tumor; VEGFRI; Osteoarticular system; Mammary gland diseases; Cancerology; Vascular endothelium growth factor; Bone; Vascular endothelial growth factor receptor 2
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/sj.bjc.6602417

Vascular endothelial growth factor (VEGF) is a proangiogenic cytokine that is expressed highly in many solid tumours often correlating with a poor prognosis. In this study, we investigated the expression of VEGF and its receptors in bone metastases from primary human breast tumours and further characterised its effects on osteoclasts in vitro. Breast cancer metastases to bone were immunohistochemically stained for VEGF, its receptors VEGFR1 and 2 (vascular endothelial growth factor receptor 1 and 2), demonstrating that breast cancer metastases express VEGF strongly and that surrounding osteoclasts express both VEGFR1 and VEGFR2. RAW 264.7 cells (mouse monocyte cell line) and human peripheral blood mononuclear cells (PBMCs) were cultured with VEGF, RANKL and M-CSF. VEGF and RANKL together induced differentiation of multinucleated, tartrate-resistant acid phophatase (TRAP)-positive cells in similar numbers to M-CSF and RANKL. The PBMCs were also able to significantly stimulate resorption of mineralised matrix after treatment with M-CSF with RANKL and VEGF with RANKL. We have shown that VEGF in the presence of RANKL supports PBMC differentiation into osteoclast-like cells, able to resorb substrate. Vascular endothelial growth factor may therefore play a role in physiological bone resorption and in pathological situations. Consequently, VEGF signalling may be a therapeutic target for osteoclast inhibition in conditions such as tumour osteolysis.