Immunogenic properties of renal cell carcinoma and the pathogenesis of osteolytic bone metastases

Int J Oncol. 2009 May;34(5):1387-93.

Abstract

The immunogenic properties of renal cell carcinoma (RCC) on bone osteolysis were investigated. mRNA expression of three proinflammatory cytokines, monocyte chemotactic protein-1 (MCP-1), interleukin-6 (IL-6) and interleukin-8 (IL-8), were determined in a panel of RCC lines (CRBM 1990, ACHN and Caki-1). Moreover proinflammatory cytokine mRNA expression and protein levels of adhesion molecules, intercellular adhesion molecule-1 (ICAM-1) and E-selectin, on human umbilical vein endothelial cells (HUVEC) incubated with the conditioned media from RCC lines were evaluated. RCC express mRNA of MCP-1, IL-6 and IL-8 that may induce a proinflammatory phenotype in endothelial cells. mRNA expression of IL-6, and IL-8 was induced on HUVEC treated with the conditioned media from RCC lines and mRNA and protein levels of ICAM-1 and E-selectin were also increased. This study demonstrates the immunogenic properties of renal cell carcinoma, such as pro-inflammatory cytokine secretion and the induction of adhesion molecules (ICAM-1 and E-Sel) by endothelial cells. ICAM-1 binds lymphocyte function-associated antigen-1 (LFA-1), which is expressed by pre-osteoclasts, so that, the observed proinflammatory phenotype in HUVEC may also favour osteoclast recruitment in bone metastases microenvironment. Osteolysis in bone metastases, mediated by this pathway, may be further potentiated by the pro-angiogenic properties of RCC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bone Neoplasms / etiology*
  • Bone Neoplasms / genetics
  • Bone Neoplasms / metabolism
  • Bone Neoplasms / secondary
  • Carcinoma, Renal Cell / genetics
  • Carcinoma, Renal Cell / immunology*
  • Carcinoma, Renal Cell / metabolism
  • Carcinoma, Renal Cell / pathology
  • Cells, Cultured
  • Culture Media, Conditioned / pharmacology
  • Cytokines / genetics
  • Cytokines / metabolism
  • Cytokines / pharmacology
  • E-Selectin / genetics
  • E-Selectin / metabolism
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism
  • Gene Expression Regulation / drug effects
  • Humans
  • Inflammation Mediators / metabolism*
  • Inflammation Mediators / pharmacology
  • Intercellular Adhesion Molecule-1 / genetics
  • Intercellular Adhesion Molecule-1 / metabolism
  • Kidney Neoplasms / genetics
  • Kidney Neoplasms / immunology*
  • Kidney Neoplasms / metabolism
  • Kidney Neoplasms / pathology
  • Models, Biological
  • Osteolysis / etiology*
  • Vascular Cell Adhesion Molecule-1 / genetics
  • Vascular Cell Adhesion Molecule-1 / metabolism

Substances

  • Culture Media, Conditioned
  • Cytokines
  • E-Selectin
  • Inflammation Mediators
  • Vascular Cell Adhesion Molecule-1
  • Intercellular Adhesion Molecule-1