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

CD105 (endoglin), a receptor for transforming growth factor (TGF) beta 1 an d beta 3 in vascular endothelial cells, is highly up-regulated in blood ves sels of tissues where neovascularisation occurs. It modulates endothelial-m esenchymal signalling and is essential for angiogenesis, Indeed, CD105 knoc kout mice die from malvascularisation by 11.5 day p.c. In the present study CD105, TGF beta 1 and CD105/TGF beta 1 complexes were quantified in plasma samples from 77 healthy individuals and 92 patients with early stage breas t: cancer prior to any treatment. When compared with normal controls, both CD105 and CD105/TGF beta 1 complex levels were significantly elevated in br east cancer patients, whereas TGF beta 1 levels were lower in cancer patien ts. The most important finding to emerge was that CD105 levels were signifi cantly increased in patients who developed distant metastasis compared with disease-free patients. While there was no significant difference between C D105 levels in controls compared to disease-free patients, it was significa ntly 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/TGF beta 1 complex nor TGF beta 1 levels correlate d 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.