Secreted frizzled related protein (sFRP)-2 inhibits bone formation and promotes cell proliferation in ameloblastoma

• Published in: Oral oncology 2009-10, Vol.45 (10), p.856-860
• Main Authors: Sathi, Gulsan Ara, Inoue, Miho, Harada, Hidemitsu, Rodriguez, Andrea P, Tamamura, Ryo, Tsujigiwa, Hidetsugu, Borkosky, Silvia S, Gunduz, Mehmet, Nagatsuka, Hitoshi
• Format: Article
• Language: English
• Subjects: Alkaline Phosphatase - metabolism; AM-1 cells; Ameloblastoma - metabolism; Amelolastoma; Biological and medical sciences; Calcification, Physiologic - drug effects; Calcification, Physiologic - physiology; Cell Line, Tumor; Cell Proliferation; Enzyme Induction; Facial bones, jaws, teeth, parodontium: diseases, semeiology; Hematology, Oncology and Palliative Medicine; Humans; Jaw Neoplasms - metabolism; KUSA/A1 cells; Medical sciences; Membrane Proteins - physiology; Membrane Proteins - secretion; Mineralized bone matrix; Neoplasm Proteins - physiology; Neoplasm Proteins - secretion; Osteoblasts - physiology; Osteogenesis - physiology; Otolaryngology; Otorhinolaryngology. Stomatology; sFRP-2; Tumors; Wnt Proteins - antagonists & inhibitors; Wnt-canonical pathway
• ISSN: 1368-8375; 1879-0593
• DOI: 10.1016/j.oraloncology.2009.02.001

Summary 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.