Secreted frizzled related protein (sFRP)-2 inhibits bone formation and promotes cell proliferation in ameloblastoma.
Secreted frizzled related protein (sFRP)-2, a Wnt antagonist, was strongly expressed by both stromal and tumor cells of ameloblastoma. The aim of this study is to evaluate whether sFRP-2 secreted from tumor cells have any direct role in suppressed bone formation or not. A pre-osteoblastic cell line, KUSA/A1 cells, cultured in conditioned medium of an ameloblastoma-derived cell line (AM-1CM) was used in the study. Alkaline phosphatase (ALP) activity, alizarin red staining, mineral quantification and MTS assay was performed. Wnt-canonical pathway is a major pathway for osteoblasts. Antagonists of this pathway, sFRP-1, 2 and 3, were detected by immunohistochemistry and western blot analysis. KUSA/A1 cells cultured in AM-1CM showed high cell proliferation, low ALP activity without mineralized matrix deposition. sFRP-2 was strongly expressed in ameloblastoma tissue and AM-1 cells. After sFRP-2 depletion, the cells showed diffuse mineralization. In this study, it was confirmed that ameloblastoma cells have a major role in decreased bone formation by secreting sFRP-2 in cell culture model. Though, sFRP-2 has great effect on tumor progression, inhibition of sFRP-2's anti-bone formation activity and cell proliferative activity may reduce the invasive property of ameloblastoma and possibility of recurrence rate.
Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikata-cho, Okayama 700-8558, Japan.
Gulsan Ara
GA
Sathi
Miho
M
Inoue
Hidemitsu
H
Harada
Andrea P
AP
Rodriguez
Ryo
R
Tamamura
Hidetsugu
H
Tsujigiwa
Silvia S
SS
Borkosky
Mehmet
M
Gunduz
Hitoshi
H
Nagatsuka
D000469:Alkaline Phosphatase / Q000378:metabolism; D000564:Ameloblastoma / Q000378:metabolism*; D002113:Calcification, Physiologic / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004790:Enzyme Induction; D006801:Humans; D007573:Jaw Neoplasms / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism / Q000502:physiology*; D009363:Neoplasm Proteins / Q000378:metabolism / Q000502:physiology*; D010006:Osteoblasts / Q000502:physiology; D010012:Osteogenesis / Q000502:physiology*; D051153:Wnt Proteins / Q000037:antagonists & inhibitors; D000094742:Secreted Frizzled-Related Proteins
D000469:Alkaline Phosphatase; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D051153:Wnt Proteins; C109618:SFRP2 protein, human; D000094742:Secreted Frizzled-Related Proteins