ODAM Expression Inhibits Human Breast Cancer Tumorigenesis

Abstract

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) inhibits growth and migration of human melanoma cells and elicits PTEN elevation and inactivation of PI3K/AKT signaling

“…The A375 melanoma cell line and BT-549 breast cancer line were obtained from the American Type Culture Collection (Rockville, MD). Control and ODAM-expressing MDA-MB-231 cells were described in detail previously [18]. All cell cultures were maintained in DMEM/F12 medium (Lonza, Walkersville, MD) containing 5% fetal bovine serum (FBS, Thermo-Fisher-Hyclone, Logan, UT), and penicillin/streptomycin (Thermo-Fisher, Pittsburg, PA) in a humidified incubator at 37°C under 5% CO 2 .…”

“…In breast cancer patient biopsies a correlation was observed between ODAM expression/localization and disease staging/clinical outcome, indicating that ODAM may serve as a novel prognostic biomarker in this type of cancer [17]. When stably transfected with recombinant ODAM the MDA-MB-231 breast cancer cell line showed marked inhibition of neoplastic and metastatic properties in vivo and in vitro [18]. This suggests that ODAM has a potentially significant role in regulating tumorigenesis and metastasis in breast cancer with possible clinical implications.…”

Inactivation of the Odontogenic ameloblast-associated gene affects the integrity of the junctional epithelium and gingival healing

“…Indeed, molars in the Amtn KO did not show aberrant abrasion . Kestler et al (2011) reported that ODAM limits the growth of breast cancer and human melanoma (Foster et al, 2013) cells and could therefore act as an inhibitor of tumour development. However, they noted that their findings are inconsistent with the apparent high levels of expression in more advanced malignancies (Siddiqui et al, 2009).…”

“…Surprisingly, ODAM is also highly upregulated in a number of epithelial cancers whose tissues of origin do not produce the protein, and it has been suggested that it may have a functional role in the pathogenesis of epithelial malignancies (Aung et al, 2006;Kestler et al, 2011;Kestler et al, 2008;Siddiqui et al, 2009). Its association with cells and extracellular matrix (the BL) and its temporo-spatial RM Wazen et al…”

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

“…In ameloblasts, nuclear Odam has been reported as a regulator of the expression of matrix metalloproteinase-20 (MMP-20), a gene that is responsible for the mineralization of enamel (Lee et al, 2010a). Also, Odam is expressed in malignant ameloblasts and other types of human neoplastic cells, including those of gastric, lung, and breast origins but the precise function of Odam in these cancers is not known (Kestler et al, 2011). Possibly, it is regulating the MMPs involved in the cancer metastasis.…”