Angiogenic characteristics of circulating and tumoural thrombospondin-1 in breast cancer

Abstract

In cancer models, thrombospondin-1 (TSP-1) has been shown to inhibit angiogenesis or promote metastasis by increasing adhesion of malignant cells to endothelium. To determine the role of TSP-1 in breast cancer and breast cancer angiogenesis, we have measured TSP-1 in plasma and tumour cytosols and compared levels to established clinicopathological prognostic parameters and intratumoural microvessel density. TSP-1 was measured, by radioimmunoassay, in plasma (pTSP-1) and tumour cytosols (cTSP-1) of women with early breast cancer (EBC) (n=71). pTSP-1 in EBC was compared to pTSP-1 levels in women with advanced breast cancer (ABC) (n=66), normal controls (n=77) and was correlated with prognostic features and microvessel density (MVD) (measured by CD31 immunostaining). cTSP-1 levels were compared to prognostic features and microvessel density. pTSP-1 in women with EBC (median 484, IQR 344-877 ng/ml) and ABC (median 588, IQR 430-952 ng/ml) were elevated when compared to normal controls (median 21, IQR 175-247) (p<0.001). Women with lymph node metastases (n=35) had higher levels of TSP-1 (median 799 ng/ml, IQR 455-943) than women who were node negative (median 343 ng/ml, IQR 267-514) (n=36) (p<0.05). Levels of pTSP-1 in EBC correlated with MVD (R=0.39, p<0.05). Levels of TSP-1 in tumour cytosols of women with EBC (median 1714, IQR 893-5283 ng/ml) correlated with microvessel density (R=0.46, p<0.01). Circulating levels of TSP-1 appear to be a marker of breast cancer aggressiveness and in breast cancer may have a pro-angiogenic rather than anti-angiogenic role.