Abstract
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.
2009 Elsevier Ireland Ltd. All rights reserved.
Publication types
-
Research Support, N.I.H., Extramural
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Antibodies
-
Bone Neoplasms / blood supply
-
Bone Neoplasms / drug therapy
-
Bone Neoplasms / enzymology*
-
Bone Neoplasms / secondary
-
Breast Neoplasms / pathology*
-
Cathepsin G / antagonists & inhibitors
-
Cathepsin G / metabolism*
-
Cell Line, Tumor
-
Chemokine CCL2 / genetics
-
Chemokine CCL2 / metabolism*
-
Female
-
Gene Expression Regulation, Neoplastic
-
Mice
-
Mice, Inbred BALB C
-
Neovascularization, Pathologic / enzymology*
-
Neovascularization, Pathologic / pathology
-
Neovascularization, Pathologic / prevention & control
-
RNA, Messenger / metabolism
-
Serine Proteinase Inhibitors / pharmacology
-
Signal Transduction* / drug effects
-
Tosylphenylalanyl Chloromethyl Ketone / pharmacology
-
Transforming Growth Factor beta / immunology
-
Transforming Growth Factor beta / metabolism*
-
Up-Regulation
-
Vascular Endothelial Growth Factor A / genetics
-
Vascular Endothelial Growth Factor A / metabolism*
Substances
-
Antibodies
-
Ccl2 protein, mouse
-
Chemokine CCL2
-
RNA, Messenger
-
Serine Proteinase Inhibitors
-
Transforming Growth Factor beta
-
Vascular Endothelial Growth Factor A
-
vascular endothelial growth factor A, mouse
-
Tosylphenylalanyl Chloromethyl Ketone
-
Cathepsin G
-
Ctsg protein, mouse