Serum soluble vascular cell adhesion molecule-1: Role as a surrogate marker of angiogenesis

Background: Angiogenesis, the development of new blood vessels from pre-exi sting vasculature, is a prerequisite for tumor growth and metastasis. Surro gate markers for angiogenesis would be useful for studying the effectivenes s of antiangiogenesis drugs. We examined the potential of three serum glyco proteins-vascular cell adhesion molecule-1 (VCAM-1), endothelial selectin ( E-selectin), and von Willebrand factor (VWF)-to serve as markers for angiog enesis. Methods: Preoperative serum levels of VCAM-1, E-selectin, and VWF w ere measured by enzyme-linked immunosorbent assay in 93 women with early br east cancer and were compared with microvessel density in each tumor, histo logic features, and recurrence after surgery, Serum samples were taken from 55 women with advanced breast cancer who were commencing hormonal therapy, both immediately before therapy and 3 months later. Changes in serum level s of VCAM-1, E-selectin, and VWF were compared with the response of the dis ease to hormonal therapy assessed 6 months after the start of hormone thera py or at disease progression. All P values are two-sided. Results: In women with early breast cancer, serum levels of VCAM-1 (but not of E-selectin or VWF) correlated closely with microvessel density in tumors (r = .65; P < . 001), and women who developed early recurrence had higher preoperative leve ls of serum VCAM-1 than those who remained disease free (P = .01), Serum VC AM-1 levels rose in women with advanced breast cancer whose disease progres sed (P < .001) but remained unchanged or fell in women with advanced breast cancer whose disease remained stable or showed a partial response to hormo nal therapy. Conclusion: Serum VCAM-1 appears to be a surrogate marker of a ngiogenesis in breast cancer. Its measurement may, therefore, help in the a ssessment of antiangiogenesis drugs currently in phase II trials.