Expression of Odontogenic Ameloblast-Associated Protein (ODAM) in Dental and Other Epithelial Neoplasms

Abstract

We previously have communicated our discovery that the amyloid associated with calcifying epithelial odontogenic tumors is composed of N-terminal fragments of the structurally novel odontogenic ameloblast-associated protein designated ODAM. Subsequently, it was shown by other investigators that ODAM is expressed in rodent enamel organ and is likely involved in dental development. We now report that this molecule also is found in certain human tissues, principally the salivary gland and trachea, as evidenced by RNA array analysis and immunohistochemistry-utilizing antibodies prepared against synthetic ODAM-related peptides and recombinant protein. Notably, these reagents immunostained normal and malignant ameloblasts and other types of human neoplastic cells, including those of gastric, lung, and breast origin where the presence in the latter was confirmed by in situ hybridization using gene-specific molecular probes. Moreover, significant titers of anti-ODAM IgG antibodies were detected in the sera of patients with these malignancies. Our studies have provided the first evidence in humans for the cellular expression of ODAM in normal and diseased states. Based on our findings, we posit that ODAM is a developmental antigen that has an essential role in tooth maturation and in the pathogenesis of certain odontogenic and other epithelial neoplasms; further, we suggest that ODAM may serve as a novel prognostic biomarker, as well as a potential diagnostic and therapeutic target for patients with breast and other epithelial forms of cancer.

Odontogenic Fibroma, Including Amyloid and Ossifying Variants

“…Congo red staining for assessment of amyloid green birefringence under crossed polars was performed on the 4 instances of amyloid associated OdonF. Immunoperoxidase staining for odontogenic ameloblast-associated protein (ODAM) was conducted in Dr. Alan Solomon's laboratory (University of Tennessee Center for Health Sciences, Department of Medicine) employing an antibody against ODAM protein, as previously described [3][4][5][6].…”

“…The presence of an amyloid-like protein deposit adjacent to epithelial elements in developing tooth germs is well documented by Congo red staining and demonstration of green birefringence under polarized light [3][4][5][6]. Biochemical analysis has been undertaken and this protein is referred to as ODAM (odontogenic ameloblast-associated protein).…”

“…Amyloid-like protein is produced by developing tooth germs and by odontogenic epithelium in the calcifying epithelial odontogenic tumor (Pindborg tumor) [3,4]. This amyloid protein has been termed odontogenic ameloblast-associated protein (ODAM) derived from a locus that encodes a 279-residue polypeptide [5,6]. The histopathologic features of these variants are detailed along with immunohistochemical profiling and amyloid staining.…”

Odontogenic ameloblast-associated and amelotin are novel basal lamina components

“…Both are expressed mainly in the tooth where they are localized at cell-tooth interfaces (Moffatt et al 2006b(Moffatt et al , 2008Nishio et al 2010;Iwasaki et al 2005;Park et al 2007;SomogyiGanss et al 2011). ODAM was also shown to be highly expressed in some epithelial malignancies but not in corresponding healthy tissues Kestler et al 2008;Siddiqui et al 2009). ODAM and AMTN proteins are encoded by two genes that are members of the secretory calcium-binding phosphoprotein (SCPP) gene cluster (Moffatt et al 2006a).…”

An evolutionarily conserved non-coding element in casein locus acts as transcriptional repressor

“…Further studies using gene knockout models may help in validating this hypothesis. Odam expression has been found in many kinds of tumours although its precise role in tumour progression is not clear (Kestler et al, 2008;Lee et al, 2010b). However, its role in regulating the expression of MMP-20, a matrix metalloproteinase involved in teeth mineralisation, has been proven (Lee et al, 2010a).…”