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

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.