TY - JOUR
T1 - Secreted frizzled related protein (sFRP)-2 inhibits bone formation and promotes cell proliferation in ameloblastoma
AU - Sathi, Gulsan Ara
AU - Inoue, Miho
AU - Harada, Hidemitsu
AU - Rodriguez, Andrea P.
AU - Tamamura, Ryo
AU - Tsujigiwa, Hidetsugu
AU - Borkosky, Silvia S.
AU - Gunduz, Mehmet
AU - Nagatsuka, Hitoshi
N1 - Funding Information:
This study was supported by Grants-in-Aid for scientific researches from the Japanese Ministry of Education, Culture, Sports, Science and Technology [19592109,17406027,20791337,20592349]
PY - 2009/10
Y1 - 2009/10
N2 - 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.
AB - 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.
KW - AM-1 cells
KW - Amelolastoma
KW - KUSA/A1 cells
KW - Mineralized bone matrix
KW - Wnt-canonical pathway
KW - sFRP-2
UR - http://www.scopus.com/inward/record.url?scp=67749150046&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=67749150046&partnerID=8YFLogxK
U2 - 10.1016/j.oraloncology.2009.02.001
DO - 10.1016/j.oraloncology.2009.02.001
M3 - Article
C2 - 19362047
AN - SCOPUS:67749150046
VL - 45
SP - 856
EP - 860
JO - Oral Oncology
JF - Oral Oncology
SN - 1368-8375
IS - 10
ER -
