tosylphenylalanyl-chloromethyl-ketone and Bone-Neoplasms

Transforming growth factor (TGF)-beta signaling makes a significant contribution to the pathogenesis of breast cancer bone metastasis. In other tumor types, TGF-beta has been shown to promote tumor vascularity. Here, we report that inhibition of TGF-beta significantly reduces microvessel density in mammary tumor-induced bone lesions, mediated by decreased expression of both vascular endothelial growth factor (VEGF) and monocyte chemotactic protein (MCP)-1, both known angiogenic factors. Cathepsin G upregulation at the tumor-bone interface has been linked to increased TGF-beta signaling, and we also report that inhibition of Cathepsin G reduced tumor vascularity, as well as VEGF and MCP-1 expression.

Topics: Animals; Antibodies; Bone Neoplasms; Breast Neoplasms; Cathepsin G; Cell Line, Tumor; Chemokine CCL2; Female; Gene Expression Regulation, Neoplastic; Mice; Mice, Inbred BALB C; Neovascularization, Pathologic; RNA, Messenger; Serine Proteinase Inhibitors; Signal Transduction; Tosylphenylalanyl Chloromethyl Ketone; Transforming Growth Factor beta; Up-Regulation; Vascular Endothelial Growth Factor A