Reduced tumourigenicity of EG7 after RANTES gene transfer and the underlying mechanism

Abstract

Introduction: Chemokine ligand 5, also known as CCL5 or regulated on activation normal T-cell expressed and secreted (RANTES), is a chemokine expressed in inflamed tissue and capable of inducing migration of immature dendritic cells (DCs) or Langerhans cells. In this study, we explored the effect of RANTES on EG7 cells. Material and methods: In vivo, RANTES gene transfer reduced the tumourigenic capacity of EG7 and prolonged the survival of tumour-bearing mice. To reveal the underlying mechanism, we performed the following experiments and provided evidence to support our hypothesis of RANTES gene therapy for EG7. Higher natural killer (NK) cell and cytotoxic T lymphocyte (CTL) activity was induced after RANTES gene transfer, accompanied by higher levels of Th1 type cytokines (IL-2 and IFN-γ). Results: Tumour necrosis was also markedly observed in the tumour tissues after RANTES gene transfer, which was attributed to reduced expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinase (MMP-2). Conclusions: We draw the conclusion that reduced tumourigenicity of EG7 after RANTES gene transfer can be attributed to higher NK cell and CTL activity, antiangiogenesis and higher levels of Th1 type cytokines induced by RANTES. These results support the notion that higher chemokine expression in tumour tissue elicits potent anti-tumour immunity. Copyright © 2010 Termedia & Banach.