title: 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.
authors.affiliation: Department of Surgery, South Manchester University Hospitals, Wythenshawe Hospital, Manchester, UK.
authors.forename: G J
authors.initials: GJ
authors.lastname: Byrne
authors.forename: K E
authors.initials: KE
authors.lastname: Hayden
authors.forename: G
authors.initials: G
authors.lastname: McDowell
authors.forename: H
authors.initials: H
authors.lastname: Lang
authors.forename: C C
authors.initials: CC
authors.lastname: Kirwan
authors.forename: L
authors.initials: L
authors.lastname: Tetlow
authors.forename: S
authors.initials: S
authors.lastname: Kumar
authors.forename: N J
authors.initials: NJ
authors.lastname: Bundred
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000098:blood supply* / Q000737:chemistry / Q000473:pathology; D003600:Cytosol / Q000737:chemistry; D005260:Female; D006801:Humans; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000209:etiology*; D019700:Thrombospondin 1 / Q000032:analysis / Q000097:blood / Q000502:physiology*
chemical_list: D019700:Thrombospondin 1