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We have posited that Odontogenic Ameloblast Associated Protein (ODAM) serves as a novel prognostic biomarker in breast cancer and now have investigated its potential role in regulating tumor growth and metastasis. Human breast cancer MDA-MB-231 cells were transfected with a recombinant ODAM plasmid construct (or, as a control, the plasmid vector alone). ODAM expression increased adhesion and apoptosis of the transfected MDA-MB-231 cells and suppressed their growth rate, migratory activity, and capability to invade extracellular matrix-coated membranes. Implantation of such cells into mouse mammary fat pads resulted in significantly smaller tumors than occurred in animals that received control cells; furthermore, ODAM-expressing cells, when injected intravenously into mice, failed to metastasize, whereas the control-transfected counterparts produced extensive lung lesions. Our finding that induction of ODAM expression in human breast cancer cells markedly inhibited their neoplastic properties provides further evidence for the regulatory role of this molecule in tumorigenesis and, consequently, is of potential clinical import.

Odontogenic Ameloblast Associated Protein (ODAM) is a protein isolated in ameloblasts during odontogenesis. ODAM expression was identified in breast cancer, but its significance remains unknown. The purpose of this study is to determine if ODAM expression can serve as a prognostic marker and provide information regarding treatment in human breast cancer. Breast cancer patients were identified from our tumor registry from 1993 to 2003. Archived breast cancer tissue from 243 patients (stage 0 = 53, stage I = 51, stage II = 53, stage III = 47, stage IV = 39) was stained using monoclonal antibody for ODAM. Presence or absence of immunostaining was correlated with stage, histologic grade, response to chemotherapy, and survival using χ2 and logistic regression analyses. Tumor nuclear staining for ODAM increased with increasing group stage ( P < 0.001). Staining for ODAM did not correlate with histologic grade or chemotherapy ( P = 0.558, P = 0.093). Improved outcomes within each stage were noted with ODAM staining, statistically significant for stages 0, I, and II ( P < 0.001, P = 0.003, P = 0.003) and underpowered for stages III and IV ( P = 0.724, P = 0.059). Survival benefit associated with tumor nuclear staining increased with advancing stage ( P < 0.001). These results show that ODAM predicts survival in breast cancer. Research is ongoing to determine ODAM's clinical utility and role in carcinogenesis.

BackgroundThe Odontogenic Ameloblast-associated Protein (ODAM) is expressed in a wide range of normal epithelial, and neoplastic tissues, and we have posited that ODAM serves as a novel prognostic biomarker for breast cancer and melanoma. Transfection of ODAM into breast cancer cells yields suppression of cellular growth, motility, and in vivo tumorigenicity. Herein we have extended these studies to the effects of ODAM on cultured melanoma cell lines.MethodsThe A375 and C8161 melanoma cell lines were stably transfected with ODAM and assayed for properties associated with tumorigenicity including cell growth, motility, and extracellular matrix adhesion. In addition, ODAM–transfected cells were assayed for signal transduction via AKT which promotes cell proliferation and survival in many neoplasms.ResultsODAM expression in A375 and C8161 cells strongly inhibited cell growth and motility in vitro, increased cell adhesion to extracellular matrix, and yielded significant cytoskeletal/morphologic rearrangement. Furthermore, AKT activity was downregulated by ODAM expression while an increase was noted in expression of the PTEN (phosphatase and tensin homolog on chromosome 10) tumor suppressor gene, an antagonist of AKT activation. Increased PTEN in ODAM-expressing cells was associated with increases in PTEN mRNA levels and de novo protein synthesis. Silencing of PTEN expression yielded recovery of AKT activity in ODAM-expressing melanoma cells. Similar PTEN elevation and inhibition of AKT by ODAM was observed in MDA-MB-231 breast cancer cells while ODAM expression had no effect in PTEN-deficient BT-549 breast cancer cells.ConclusionsThe apparent anti-neoplastic effects of ODAM in cultured melanoma and breast cancer cells are associated with increased PTEN expression, and suppression of AKT activity. This association should serve to clarify the clinical import of ODAM expression and any role it may serve as an indicator of tumor behavior.