IL-17A Stimulates the Progression of Giant Cell Tumors of Bone
A partir d'échantillons tumoraux prélevés sur 74 patients atteints d'une tumeur osseuse à cellules géantes, cette étude met en évidence des mécanismes par lesquels l'interleukine 17A favorise la croissance tumorale
Purpose:Giant cell tumors of bone (GCTBs) exhibit aggressive bone lytic behavior. Studies have shown that interleukin 17A (IL-17A) is involved pathological bone resorption in various skeletal disorders. Thus, we have investigated the role of IL-17A in GCTBs.
Experimental Design:We evaluated the progression of GCTBs using Campanacci grading and Enneking staging systems in 74 GCTB patients. The expression of IL-17A and the IL-17A receptor A (IL-17RA) was assessed in GCTB tissues and in both multinucleated giant cells (MNGCs) and stromal cells (SCs) cultured in vitro using immunostaining and RT-PCR. The effects of IL-17A on the osteolytic activity of the MNGCs and the proliferation of the SCs were investigated using the "pit" formation and MTT assays, respectively. The effects of IL-17A on the expression of pro-osteolytic factors were examined in primary cultured MNGCs and SCs using RT-PCR, Western blotting, and gene expression microarrays.
Results:In GCTBs, we detected abundant levels of IL-17A, which were associated with tumor extension and grade. IL-17A is predominantly produced by MNGCs, whereas IL-17RA is expressed by both MNGCs and SCs in GCTBs. In the MNGCs, the IL-17A increased the mRNA expression of IL-17A and pro-osteolytic enzymes, also enhanced osteolytic ability. In the SCs, the IL-17A stimulated cellular proliferation and the expression of pro-osteolytic factors, including RANKL through myc and STAT3, respectively. In addition, IL-17A stimulated in vivo tumor growth and the extent of angiogenesis in GCTBs.
Conclusions:IL-17A stimulates the progression of GCTBs and might represent a useful candidate marker for progression and as a therapeutic target for GCTBs.