title: The Calcium-Binding Protein S100A6 Accelerates Human Osteosarcoma Growth by Promoting Cell Proliferation and Inhibiting Osteogenic Differentiation.
abstract: OBJECTIVE
  Although osteosarcoma (OS) is the most common primary malignancy of bone, its molecular pathogenesis remains to be fully understood. We previously found the calcium-binding protein S100A6 was expressed in ∼80% of the analyzed OS primary and/or metastatic tumor samples. Here, we investigate the role of S100A6 in OS growth and progression.
  
  
  METHODS
  S100A6 expression was assessed by qPCR and Western blotting. Overexpression or knockdown of S100A6 was carried out to determine S100A6's effect on proliferation, cell cycle, apoptosis, tumor growth, and osteogenic differentiation.
  
  
  RESULTS
  S100A6 expression was readily detected in human OS cell lines. Exogenous S100A6 expression promoted cell proliferation in vitro and tumor growth in an orthotopic xenograft model of human OS. S100A6 overexpression reduced the numbers of OS cells in G1 phase and increased viable cells under serum starvation condition. Conversely, silencing S100A6 expression induced the production of cleaved caspase 3, and increased early stage apoptosis. S100A6 knockdown increased osteogenic differentiation activity of mesenchymal stem cells, while S100A6 overexpression inhibited osteogenic differentiation. BMP9-induced bone formation was augmented by S100A6 knockdown.
  
  
  CONCLUSIONS
  Our findings strongly suggest that S100A6 may promote OS cell proliferation and OS tumor growth at least in part by facilitating cell cycle progression, preventing apoptosis, and inhibiting osteogenic differentiation. Thus, it is conceivable that targeting S100A6 may be exploited as a novel anti-OS therapy.
authors.forename: Yasha
authors.initials: Y
authors.lastname: Li
authors.forename: Eric R
authors.initials: ER
authors.lastname: Wagner
authors.forename: Zhengjian
authors.initials: Z
authors.lastname: Yan
authors.forename: Zhonliang
authors.initials: Z
authors.lastname: Wang
authors.forename: Gaurav
authors.initials: G
authors.lastname: Luther
authors.forename: Wei
authors.initials: W
authors.lastname: Jiang
authors.forename: Jixing
authors.initials: J
authors.lastname: Ye
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wei
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Lianggong
authors.initials: L
authors.lastname: Zhao
authors.forename: Shun
authors.initials: S
authors.lastname: Lu
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.forename: Maryam K
authors.initials: MK
authors.lastname: Mohammed
authors.forename: Shengli
authors.initials: S
authors.lastname: Tang
authors.forename: Hao
authors.initials: H
authors.lastname: Liu
authors.forename: Jiaming
authors.initials: J
authors.lastname: Fan
authors.forename: Fugui
authors.initials: F
authors.lastname: Zhang
authors.forename: Yulong
authors.initials: Y
authors.lastname: Zou
authors.forename: Dongzhe
authors.initials: D
authors.lastname: Song
authors.forename: Junyi
authors.initials: J
authors.lastname: Liao
authors.forename: Rex C
authors.initials: RC
authors.lastname: Haydon
authors.forename: Hue H
authors.initials: HH
authors.lastname: Luu
authors.forename: Tong-Chuan
authors.initials: TC
authors.lastname: He
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology*; D064593:Heterografts; D006801:Humans; D051379:Mice; D010012:Osteogenesis; D012516:Osteosarcoma / Q000473:pathology*; D000075383:S100 Calcium Binding Protein A6; D009418:S100 Proteins / Q000502:physiology*
chemical_list: D018797:Cell Cycle Proteins; D000075383:S100 Calcium Binding Protein A6; D009418:S100 Proteins; C055351:S100A6 protein, human