Odontogenic Ameloblast-Associated Protein (Odam) Alters The Growth And Migration Of Human Melanoma Cells

Abstract Initial studies of the Odontogenic Ameloblast-Associated Protein (ODAM) revealed that it is highly expressed in mature ameloblasts and is present in the rodent enamel organ and junctional epithelium. Further analysis showed that ODAM is expressed in several epithelial malignancies including gastric, colon, breast, lung and melanoma. A correlation was observed between ODAM expression/localization and breast cancer stage/clinical patient outcome, indicating that ODAM may serve as a novel prognostic biomarker in this type of cancer. When transfected with rODAM and injected into mice intravenously, the MDA-MB-231 breast cancer cell line showed marked inhibition of neoplastic and metastatic properties. This suggests that ODAM has a potentially significant regulatory role in tumorigenesis and metastasis of breast cancer with important clinical implications. To investigate the role of ODAM in melanoma, archived slides prepared from primary melanoma tissue specimens were obtained and stained with anti-ODAM antibodies and results were compared with retrospective clinical data. In patients that were found to have positive sentinel lymph nodes, ODAM localized to the nucleus in 76% of the cases. This suggests that nuclear-localization of ODAM in the primary tumor is a negative prognostic factor, which could assist in determining management of this devastating cancer. Melanoma is frequently diagnosed at late stages, often metastatic to regional lymph nodes or distant sites. The inhibition of neoplastic and metastatic properties shown in ODAM-expressing breast malignancies encouraged further investigation into the effect of ODAM expression in the tumorigenesis of melanoma. The human metastatic melanoma cell line C8161 does not express ODAM and was stably transfected with rODAM. In two consecutive growth assays, the ODAM-expressing C8161-clones showed significant growth inhibition compared to parent C8161 cells. In wound-healing assays of cell migration, exogenous rODAM was added at increasingly higher concentrations to wells of C8161 cells at 100% confluency immediately before scratch-wounding the monolayer. After twenty-four hours, C8161 parent cells had near-complete coverage of the scratch defect. In the wells with added exogenous rODAM, cells showed a decreased ability to migrate and cover the scratch, with more inhibition of migration as the concentration of rODAM increased from 3 to 12 µg/mL. These findings demonstrate that ODAM alters the behavior of the C8161 human melanoma cell line with respect to growth and cell migration. Further studies to assess tumorigenesis in vivo are under way, concerning the potential effect that ODAM may have on invasion, gene expression and metastatic characteristics of this cell line. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4302. doi:1538-7445.AM2012-4302