title: Initiation of aspirin therapy modulates angiogenic protein levels in women with breast cancer receiving tamoxifen therapy.
abstract: Aspirin has a range of antineoplastic properties linked to inhibition of cyclooxygenase enzymes in tumor cells, platelet inhibition and to inhibition of angiogenesis. We undertook a prospective study to determine the influence of a 45-day course of aspirin therapy on circulating and intraplatelet levels of selected proangiogenic (vascular endothelial growth factor [VEGF]) and antiangiogenic (thrombospondin-1 [TSP-1]) proteins, and platelet protein release in women diagnosed with breast cancer who were receiving tamoxifen therapy. Initiation of aspirin therapy increases serum and intraplatelet levels of TSP-1 without a corresponding increase in VEGF levels. Following aspirin therapy, VEGF levels decreased (relative to pretreatment levels) while TSP-1 returned to pretreatment levels. Plasma TSP-1 and VEGF levels did not change on aspirin therapy. Aspirin use also decreased thrombin receptor mediated release of TSP-1 and VEGF from platelets. The selective impact on platelet angiogenic protein content and release supports one mechanism by which aspirin can modify the angiogenic balance in women receiving tamoxifen therapy. Aspirin therapy appears to favor an overall antiangiogenic balance in women with breast cancer who are receiving tamoxifen therapy.
authors.affiliation: Department of Medicine, University of Vermont, Burlington, Vermont, USA.
authors.forename: Chris E
authors.initials: CE
authors.lastname: Holmes
authors.forename: Jagoda
authors.initials: J
authors.lastname: Jasielec
authors.forename: Jamie E
authors.initials: JE
authors.lastname: Levis
authors.forename: Joan
authors.initials: J
authors.lastname: Skelly
authors.forename: Hyman B
authors.initials: HB
authors.lastname: Muss
mesh_terms: D000328:Adult; D000368:Aged; D042501:Angiogenic Proteins / Q000097:blood*; D001241:Aspirin / Q000494:pharmacology / Q000627:therapeutic use*; D001792:Blood Platelets / Q000378:metabolism; D001943:Breast Neoplasms / Q000097:blood* / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008875:Middle Aged; D015539:Platelet Activation / Q000187:drug effects; D018179:Receptors, Thrombin / Q000378:metabolism; D013629:Tamoxifen / Q000494:pharmacology / Q000627:therapeutic use*; D019700:Thrombospondin 1 / Q000097:blood; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
chemical_list: D042501:Angiogenic Proteins; D018179:Receptors, Thrombin; D019700:Thrombospondin 1; D042461:Vascular Endothelial Growth Factor A; D013629:Tamoxifen; D001241:Aspirin
keywords: TSP-1 tamoxifen; VEGF; breast cancer; platelet activation