title: Monocyte-Induced Prostate Cancer Cell Invasion is Mediated by Chemokine ligand 2 and Nuclear Factor-κB Activity.
abstract: BACKGROUND
  The tumor microenvironment contains inflammatory cells which can influence cancer growth and progression; however the mediators of these effects vary with different cancer types. The mechanisms by which prostate cancer cells communicate with monocytes to promote cancer progression are incompletely understood. This study tested prostate cancer cell and monocyte interactions that lead to increased prostate cancer cell invasion.
  
  
  METHODS
  We analyzed the prostate cancer cell invasion and NF-κB activity and cytokine expression during interaction with monocyte-lineage cells in co-cultures. The roles of monocyte chemotactic factor (MCP-1/CCL2) and NF-κB activity for co-culture induced prostate cancer invasion were tested. Clinical prostate cancer NF-κB expression was analyzed by immunohistochemistry.
  
  
  RESULTS
  In co-cultures of prostate cancer cell lines with monocyte-lineage cells, (C-C motif) ligand 2 (CCL2) levels were significantly increased when compared with monocytes or cancer cells cultured alone. Prostate cancer cell invasion was induced by recombinant CCL2 in a dose dependent manner, similar to co-cultures with monocytes. The monocyte-induced prostate cancer cell invasion was inhibited by CCL2 neutralizing antibodies and by the CCR2 inhibitor, RS102895. Prostate cancer cell invasion and CCL2 expression induced in the co-cultures was inhibited by Lactacystin and Bay11-7082 NF-κB inhibitors. Prostate cancer cell NF-κB DNA binding activity depended on CCL2 dose and was inhibited by CCL2 neutralizing antibodies. Clinical prostate cancer NF-κB expression correlated with tumor grade.
  
  
  CONCLUSIONS
  Co-cultures with monocyte-lineage cell lines stimulated increased prostate cancer cell invasion through increased CCL2 expression and increased prostate cancer cell NF-κB activity. CCL2 and NF-κB may be useful therapeutic targets to interfere with inflammation-induced prostate cancer invasion.
authors: Department of Pathology, Northwestern University, The Feinberg School of Medicine, Chicago, USA.
authors: Paul F
authors: PF
authors: Lindholm
authors: Indigenèse Biotechnologies, Hyderabad, India.
authors: Neela
authors: N
authors: Sivapurapu
authors: Department of Preventive Medicine and Bioinformatics Core, Northwestern University, The Feinberg School of Medicine, Chicago, USA.
authors: Borko
authors: B
authors: Jovanovic
authors: Department of Pathology, University of Illinois at Chicago College of Medicine, Chicago, USA.
authors: André
authors: A
authors: Kajdacsy-Balla
keywords: Co-culture; Inflammation; MCP-1; NF-κB; Paracrine