Infantile haemangioma expresses tumour necrosis factor-related apoptosis-inducing ligand (TRAIL), TRAIL receptors, osteoprotegerin and receptor activator for nuclear factor кB ligand (RANKL)†

Abstract

To investigate the expression of tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) and its receptors and decoy receptors, including osteoprotegerin (OPG) in infantile haemangioma (IH). Immunostaining, Western blotting and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) were used on IH biopsies and haemangioma explant-derived cells (HaemEDCs). TRAIL and its receptors and decoy receptors, including OPG, are expressed in proliferating IH tissues and in HaemEDCs. Cells forming the endothelium of immature capillaries of proliferating IHs express abundant OPG and show punctate von Willebrand Factor (vWF) staining. As the cells mature and assume the characteristic of endothelial cells they increase expression of vWF, but lose expression of OPG. The endothelium of IH shows minimal expression of receptor activator for nuclear factor кB ligand (RANKL) compared with a small population of RANKL-positive cells located within the interstitium between microvessels. Proliferating HaemEDCs express significantly higher levels of OPG and decoy receptor 2 than the matched tissue samples. Increased OPG expression is detected in the extracellular matrix and in the conditioned medium of HaemEDCs. Our data suggest that OPG through the TRAIL pathway, but not the RANKL pathway, plays a role in regulating anti-apoptosis during the development of IH.