heparitin-sulfate and Ameloblastoma

AMBN (ameloblastin) is an enamel matrix protein that regulates cell adhesion, proliferation, and differentiation of ameloblasts. In AMBN-deficient mice, ameloblasts are detached from the enamel matrix, continue to proliferate, and form a multiple cell layer; often, odontogenic tumors develop in the maxilla with age. However, the mechanism of AMBN functions in these biological processes remains unclear. By using recombinant AMBN proteins, we found that AMBN had heparin binding domains at the C-terminal half and that these domains were critical for AMBN binding to dental epithelial cells. Overexpression of full-length AMBN protein inhibited proliferation of human ameloblastoma AM-1 cells, but overexpression of heparin binding domain-deficient AMBN protein had no inhibitory effect. In full-length AMBN-overexpressing AM-1 cells, the expression of Msx2, which is involved in the dental epithelial progenitor phenotype, was decreased, whereas the expression of cell proliferation inhibitors p21 and p27 was increased. We also found that the expression of enamelin, a marker of differentiated ameloblasts, was induced, suggesting that AMBN promotes odontogenic tumor differentiation. Thus, our results suggest that AMBN promotes cell binding through the heparin binding sites and plays an important role in preventing odontogenic tumor development by suppressing cell proliferation and maintaining differentiation phenotype through Msx2, p21, and p27.

Topics: Ameloblastoma; Amelogenin; Animals; Binding Sites; Cell Adhesion; Cell Line, Tumor; Cell Proliferation; Chlorocebus aethiops; COS Cells; Cyclin-Dependent Kinase Inhibitor p21; Dental Enamel Proteins; Epithelial Cells; Gene Expression Regulation, Neoplastic; Heparin; Heparitin Sulfate; Homeodomain Proteins; Humans; Mice; Protein Structure, Tertiary; Rats; Signal Transduction; Tooth; Transcriptional Activation

Bone morphogenic protein (BMP) and Wnt signaling pathway molecules play important roles in cytodifferentiation and cell proliferation. We attempted to localize these signaling molecules in the granular cell ameloblastoma.. Four samples of paraffin-embedded ameloblastoma with granular cells were studied. Immunohistochemistry was performed to detect basement membrane type heparan sulfate (HS) (JM403), cell surface type HS (10E4), heparanase, Wnt-5a, Wnt-2, beta-catenin, and BMP-4.. In all four samples, strong expression of beta-catenin and Wnt-5a was detected within the granular cells, while BMP-4 expression was weak and Wnt-2 was negative. Immunoreactivities of basement membrane type HS, cell surface type HS, and heparanase were variable within granular cells in ameloblastoma.. Granular cells in ameloblastoma exhibit abnormal biological behaviors, particularly synthesis and secretion of protein. Synthesis of signaling molecules is upregulated, but secretion is arrested in some cases, while both are lost in other cases.

Topics: Ameloblastoma; beta Catenin; Bone Morphogenetic Protein 4; Bone Morphogenetic Proteins; Glucuronidase; Heparitin Sulfate; Humans; Immunohistochemistry; Intercellular Signaling Peptides and Proteins; Proto-Oncogene Proteins; Wnt Proteins; Wnt-5a Protein

Glycosaminoglycans and proteoglycans were analysed in keratinizing and nonkeratinizing odontogenic cyst fluids. Hyaluronic acid showed the highest incidence and abundance amongst the glycosaminoglycans detected. Appreciable amounts of chondroitin-4-sulphate were also observed, particularly in the dental cysts, with lesser amounts of the other glycosaminoglycans. Heparan sulphate showed a higher incidence and abundance in the keratocyst than the other cysts, whilst chondroitin-6-sulphate could not be detected in any of the cysts. A considerable proportion of the glycosaminoglycans of the fluids appeared to be complexed with protein and was released only after proteolytic digestion. The origin of these macromolecules is uncertain although it is likely that they are derived from both the connective tissue and the epithelium of the cyst wall.

Topics: Ameloblastoma; Chondroitin Sulfates; Dentigerous Cyst; Dermatan Sulfate; Electrophoresis, Cellulose Acetate; Glycosaminoglycans; Heparitin Sulfate; Hexuronic Acids; Humans; Hyaluronic Acid; Jaw Neoplasms; Odontogenic Cysts