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

Angiogenesis, the development of new blood vessels from pre-existing vasculature, is a prerequisite for tumor growth and metastasis. Surrogate markers for angiogenesis would be useful for studying the effectiveness of antiangiogenesis drugs. We examined the potential of three serum glycoproteins-vascular cell adhesion molecule-1 (VCAM-1), endothelial selectin (E-selectin), and von Willebrand factor (VWF)-to serve as markers for angiogenesis.

Preoperative serum levels of VCAM-1, E-selectin, and VWF were measured by enzyme-linked immunosorbent assay in 93 women with early breast cancer and were compared with microvessel density in each tumor, histologic 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 levels of VCAM-1, E-selectin, and VWF were compared with the response of the disease to hormonal therapy assessed 6 months after the start of hormone therapy or at disease progression. All P: values are two-sided.

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 levels of serum VCAM-1 than those who remained disease free (P: =.01). Serum VCAM-1 levels rose in women with advanced breast cancer whose disease progressed (P:<.001) but remained unchanged or fell in women with advanced breast cancer whose disease remained stable or showed a partial response to hormonal therapy.

Serum VCAM-1 appears to be a surrogate marker of angiogenesis in breast cancer. Its measurement may, therefore, help in the assessment of antiangiogenesis drugs currently in phase II trials.