Cathepsin G-mediated enhanced TGF-beta signaling promotes angiogenesis via upregulation of VEGF and MCP-1

Cancer Lett. 2010 Feb 28;288(2):162-9. doi: 10.1016/j.canlet.2009.06.035. Epub 2009 Jul 30.

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.

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