Expression of odontogenic ameloblast-associated protein (ODAM) in dental and other epithelial neoplasms.
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.
Kestler
Daniel P
DP
Human Immunology and Cancer Program, Department of Medicine, University of Tennessee Graduate School of Medicine, Knoxville, Tennessee 37920, United States of America.
Foster
James S
JS
Macy
Sallie D
SD
Murphy
Charles L
CL
Weiss
Deborah T
DT
Solomon
Alan
A
D000565:Ameloblasts / Q000166:cytology / Q000378:metabolism*; D000595:Amino Acid Sequence; D000682:Amyloid; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D009808:Odontogenic Tumors / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000682:Amyloid; D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009363:Neoplasm Proteins; C480049:ODAM protein, human; C555400:ODAM protein, mouse; D011506:Proteins