title: IL-17A stimulates the progression of giant cell tumors of bone.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  IL-17A stimulates the progression of GCTBs and might represent a useful candidate marker for progression and as a therapeutic target for GCTBs.
authors.affiliation: Department of Orthopaedics , The General Hospital of Chinese People's Liberation Army, Beijing, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Xu
authors.forename: Zhi-Gang
authors.initials: ZG
authors.lastname: Song
authors.forename: Cheng-Xiong
authors.initials: CX
authors.lastname: Xu
authors.forename: Guang-Hua
authors.initials: GH
authors.lastname: Rong
authors.forename: Ke-Xing
authors.initials: KX
authors.lastname: Fan
authors.forename: Ji-Ying
authors.initials: JY
authors.lastname: Chen
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Jin-Peng
authors.initials: JP
authors.lastname: Jia
authors.forename: Gang
authors.initials: G
authors.lastname: Han
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Chai
authors.forename: Wen-Tao
authors.initials: WT
authors.lastname: Liang
authors.forename: Wen-Zhi
authors.initials: WZ
authors.lastname: Bi
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D001859:Bone Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D063646:Carcinogenesis / Q000235:genetics*; D049109:Cell Proliferation; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D018212:Giant Cell Tumor of Bone / Q000235:genetics* / Q000473:pathology; D006801:Humans; D020381:Interleukin-17 / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D015398:Signal Transduction / Q000235:genetics
chemical_list: C508717:IL17A protein, human; D020381:Interleukin-17