Plasma levels of soluble CD105 correlate with metastasis in patients with breast cancer

CD105 (endoglin), a receptor for transforming growth factor (TGF) β1 and β3 in vascular endothelial cells, is highly up-regulated in blood vessels of tissues where neovascularisation occurs. It modulates endothelial- mesenchymal signalling and is essential for angiogenesis. Indeed, CD105 knockout mice die from malvascularisation by 11.5 day p.c. In the present study CD 105, TGFβ1 and CD105/TGFβ1 complexes were quantified in plasma samples from 77 healthy individuals and 92 patients with early stage breast cancer prior to any treatment. When compared with normal controls, both CD 105 and CD105/TGFβ1 complex levels were significantly elevated in breast cancer patients, whereas TGFβ1 levels were lower in cancer patients. The most important finding to emerge was that CD105 levels were significantly increased in patients who developed distant metastasis compared with disease- free patients. While there was no significant difference between CD105 levels in controls compared to disease-free patients, it was significantly higher in patients with metastatic disease. Thus patients who had died following local relapse or distant metastases possessed the highest levels of CD105. Neither CD105/TGFβ1 complex nor TGFβ1 levels correlated with tumour progression. Our data indicate that CD105 might be a valuable novel angiogenic marker for identifying breast cancer patients who are at high risk of developing metastasis. (C) 2000 Wiley-Liss, Inc.