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

Aldridge, Stephen; Lennard, T. W. J.; Jl, Williams; Birch, Mark

doi:10.1038/sj.bjc.6602417

Cited by 74 publications

(47 citation statements)

References 32 publications

(27 reference statements)

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“…Increased VEGF level was also associated with biochemical markers of osteoclastic activity and bone matrix degradation, which is in agreement with a recent study showing high that VEGF stimulates osteoclastic differentiation in vitro (Aldridge et al, 2005).…”

Section: Discussionsupporting

confidence: 92%

Association of 12 serum biochemical markers of angiogenesis, tumour invasion and bone turnover with bone metastases from breast cancer: a crossectional and longitudinal evaluation

Voorzanger-Rousselot¹,

Juillet²,

Mareau³

et al. 2006

Br J Cancer

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Complex biological pathways including angiogenesis, invasion, osteoclastic activation and bone matrix degradation are involved in the formation of bone metastasis (BM). The aim of our study was to investigate the cross-sectional and longitudinal associations of a panel of 12 serum biochemical markers reflecting biological pathways underlying BM development. In a cross-sectional study, we investigated 29 patients with primary breast carcinoma without BM (BC/BMÀ), 28 patients with breast carcinoma and BM (BC/ BM þ ) and 15 healthy women. In longitudinal analyses, we investigated 34 patients for whom serum was obtained a two different time points: at the time of primary BC diagnosis and after a median time of 3 years. During this follow-up, 15 patients developed BM, whereas the other 19 remained free of BM. In patients who developed BM, the second samples were obtained before BM was documented by bone scan. The cross-sectional analyses have shown all biochemical markers to be significantly elevated in patients with BM, when compared to the patients without BM and healthy controls, except TGFb1 that was significantly decreased. Multivariable analyses showed that only the bone resorption markers TRACP 5b, CTX and ICTP, and the marker of angiogenesis VEGF were independently associated with BM. Those markers correctly distinguished 85% of BC patients with or without BM from normal individuals. Longitudinal analyses showed that patients with primary BC who developed BM during follow-up had higher levels of TRACP5b ( þ 95%, P ¼ 0.08) at the time of primary diagnosis, those patients had also a higher increases of ICTP (P ¼ 0.006), MMP-7 (P ¼ 0.004) and TIMP-1 (P ¼ 0.017) during follow-up than patients who did not progress toward bone metastasis. This study provides evidence of increase and interrelationship of circulating markers of angiogenesis, invasion and bone resorption in patients with BC with and without BM. Markers of bone resorption have the highest independent diagnostic value for detecting and potentially predicting BM in breast carcinoma patients. Bone is one of the most common sites of metastasis for certain types of tumours, especially prostate, breast and lung carcinoma (Mundy, 2002). Breast cancer progression to bone is a defining feature of a highly malignant tumour and the major cause of cancer-treatment failure. Early detection of bone metastasis is critical for clinical management and accurate staging of tumours. Currently there is no a simple way to reliably detect and predict which patients will develop bone metastasis. The detection of bone metastases relies on imaging technology, but novel approaches based on biomarker assessments are under intense investigation. Increasing body of data suggests that metastatic dissemination is site specific (Horak and Steeg, 2005) and that distinct molecular factors regulate bone metastasis formation (Yin et al, 2005). A multifactorial and multistep process of bone metastasis formation involves several biological mechanisms including angiogenesis, invasion through...

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Section: Discussionsupporting

confidence: 92%

Association of 12 serum biochemical markers of angiogenesis, tumour invasion and bone turnover with bone metastases from breast cancer: a crossectional and longitudinal evaluation

Voorzanger-Rousselot¹,

Juillet²,

Mareau³

et al. 2006

Br J Cancer

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“…The key angiogenic factor vascular endothelial growth factor-A (VEGF-A) is produced in metastatic bone lesions (9)(10)(11). Blocking VEGF-A in breast cancer bone metastasis reduces osteolytic lesions (12).…”

Section: Introductionmentioning

confidence: 99%

Anti–Placental Growth Factor Reduces Bone Metastasis by Blocking Tumor Cell Engraftment and Osteoclast Differentiation

et al. 2010

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Treatment of bone metastases is largely symptomatic and is still an unmet medical need. Current therapies mainly target the late phase of tumor-induced osteoclast activation and hereby inhibit further metastatic growth. This treatment method is, however, less effective in preventing initial tumor engraftment, a process that is supposed to depend on the bone microenvironment. We explored whether bone-derived placental growth factor (PlGF), a homologue of vascular endothelial growth factor-A, regulates osteolytic metastasis. Osteogenic cells secrete PlGF, the expression of which is enhanced by bone-metastasizing breast tumor cells. Selective neutralization of host-derived PlGF by anti-mouse PlGF (αPlGF) reduced the incidence, number, and size of bone metastases, and preserved bone mass. αPlGF did not affect metastatic tumor angiogenesis but inhibited osteoclast formation by preventing the upregulation of the osteoclastogenic cytokine receptor activator of NF-κB ligand in osteogenic cells, as well as by blocking the autocrine osteoclastogenic activity of PlGF. αPlGF also reduced the engraftment of tumor cells in the bone and inhibited their interaction with matrix components in the metastatic niche. αPlGF therefore inhibits not only the progression of metastasis but also the settlement of tumor in the bone. These findings identify novel properties of PlGF and suggest that αPlGF might offer opportunities for adjuvant therapy of bone metastasis.

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“…VEGFR1 positive haematopoietic progenitor cells are recruited to sites of future metastasis (88). VEGF receptors are expressed by breast cancer cells as well as osteoclasts and osteoclast precursors, and VEGF expression correlates to increased tumour size and grade in humans (89). In addition, we have shown that breast cancer cells secrete factors that support the subsequent attachment of breast cancer cells acting at least in part through -secretase-mediated Notch signalling (20).…”

Section: Homing Of Breast Cancer Cells To Bone 41 Creation Of the Prmentioning

confidence: 99%

Breast Cancer Metastases to Bone: Role of the Microenvironment

Fong¹,

Komarova²

2011

Breast Cancer - Focusing Tumor Microenvironment, Stem Cells and Metastasis

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

Cited by 74 publications

References 32 publications

Association of 12 serum biochemical markers of angiogenesis, tumour invasion and bone turnover with bone metastases from breast cancer: a crossectional and longitudinal evaluation

Association of 12 serum biochemical markers of angiogenesis, tumour invasion and bone turnover with bone metastases from breast cancer: a crossectional and longitudinal evaluation

Anti–Placental Growth Factor Reduces Bone Metastasis by Blocking Tumor Cell Engraftment and Osteoclast Differentiation

Breast Cancer Metastases to Bone: Role of the Microenvironment

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