IL-17A stimulates the progression of giant cell tumors of bone.

Abstract

PURPOSE Giant cell tumors of bone (GCTB) exhibit aggressive bone lytic behavior. Studies have shown that interleukin 17A (IL-17A) is involved pathologic 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 patients with GCTB. The expression of IL-17A and the IL-17A receptor A (IL-17RA) was assessed in GCTB tissues and in both multinucleated giant cells (MNGC) and stromal cells cultured in vitro using immunostaining and reverse transcription PCR (RT-PCR). The effects of IL-17A on the osteolytic activity of the MNGCs and the proliferation of the stromal cells were investigated using the "pit" formation and MTT assays, respectively. The effects of IL-17A on the expression of proosteolytic factors were examined in primary cultured MNGCs and stromal cells 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 stromal cells in GCTBs. In the MNGCs, the IL-17A increased the mRNA expression of IL-17A and proosteolytic enzymes, and also enhanced osteolytic ability. In the stromal cells, the IL-17A stimulated cellular proliferation and the expression of proosteolytic factors, including RANKL through myc and STAT3, respectively. In addition, IL-17A stimulated in vivo tumor growth and the extent of angiogenesis in GCTBs. CONCLUSION IL-17A stimulates the progression of GCTBs and might represent a useful candidate marker for progression and as a therapeutic target for GCTBs.

DOI: 10.1158/1078-0432.CCR-13-0251

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@article{Xu2013IL17AST, title={IL-17A stimulates the progression of giant cell tumors of bone.}, author={Meng Xu and Zhi-gang Song and Cheng-Xiong Xu and Guang-hua Rong and Ke-Xing Fan and Ji-ying Chen and Wei Zhang and Jin-Peng Jia and Gang Han and Wei Wang and Wei Chai and Wen-Tao Liang and Wen-Zhi Bi and Yan Wang}, journal={Clinical cancer research : an official journal of the American Association for Cancer Research}, year={2013}, volume={19 17}, pages={4697-705} }