Tamoxifen and estrogen effects on TGF-beta formation: Role of thrombospondin-1, alpha v beta 3, and integrin-associated protein

We have found that the enhanced activation of latent TGF-beta by human brea st carcinoma cell lines either treated with tamoxifen or deprived of estrog en is dependent upon thrombospondin-1 (TSP-1) since activation was blocked by anti-TSP-1 antibodies or by a TSP antagonist peptide. However, TGF-beta formation upon tamoxifen exposure to estrogen withdrawal is associated with decreased levels of soluble TSP-1. A concomitant increase in the expressio n of the TSP-1 receptors alphav beta3 and integrin-associated protein (IAP) occurs under these conditions, and antibodies to TSP-1 or to these recepto rs inhibit increased TGF-beta formation. Therefore, increased cell surface associated TSP-1 enhances latent TGF-beta activation. (C) 2001 Academic Pre ss.