title: IL-17A/IL-17RA interaction promoted metastasis of osteosarcoma cells.
abstract: Osteosarcoma (OS) is the most common human primary malignant bone tumor in children and young adults with poor prognosis because of their high metastatic potential. Identification of key factors that could regulate the aggressive biologic behavior of OS, particularly with respect to metastasis, would be necessary if significant improvements in therapeutic outcome are to occur. In this study, we carefully evaluated the potential role of IL-17A/IL-17RA interaction in metastasis of OS. We found that serum IL-17A was higher in OS patients with metastasis and was associated with their clinical stage. The elevated expression of IL-17RA was observed in tumor tissue from OS patients with metastasis. Of note, we showed that IL-17A could promote the metastasis of U-2 OS cells which expression high IL-17RA, but not MG63 cells which expression low IL-17RA. Further, we revealed that downregulation of IL-17RA in U-2 cells could abrogated the enhanced metastasis induced by IL-17A, while upregulation of IL-17RA in MG63 cells could elevate their response to IL-17A and exerted enhanced metastasis. We observed that IL-17A/IL-17RA interaction promoted the expression of VEGF, MMP9 and CXCR4 in OS cells, which might partly explain the enhanced metastasis of OS cells. Furthermore, we showed that Stat3 activity was crucial for IL-17A/IL-17RA interaction to promote OS metastasis. Finally, we confirmed that IL-17A/IL-17RA interaction promoted the metastasis of OS in nude mice. Our findings might provide a mechanistic explanation for metastasis of OS in vivo, and suggested that targeting IL-17A signaling was a novel promising strategy to treat patients with OS.
authors.affiliation: Qingdao Institute of Transfusion Medicine, Qingdao Blood Center, Shandong, China.
authors.forename: Mingmin
authors.initials: M
authors.lastname: Wang
authors.forename: Luanqiu
authors.initials: L
authors.lastname: Wang
authors.forename: Tao
authors.initials: T
authors.lastname: Ren
authors.forename: Lin
authors.initials: L
authors.lastname: Xu
authors.forename: Zhenke
authors.initials: Z
authors.lastname: Wen
mesh_terms: D000293:Adolescent; D000818:Animals; D001859:Bone Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D002648:Child; D004195:Disease Models, Animal; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020381:Interleukin-17 / Q000097:blood / Q000378:metabolism*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009362:Neoplasm Metastasis; D012516:Osteosarcoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D011485:Protein Binding; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism; D053722:Receptors, Interleukin-17 / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D042442:Vascular Endothelial Growth Factors / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
chemical_list: D020381:Interleukin-17; D019718:Receptors, CXCR4; D053722:Receptors, Interleukin-17; D050796:STAT3 Transcription Factor; D042442:Vascular Endothelial Growth Factors; D020780:Matrix Metalloproteinase 9