Odontogenic ameloblast-associated protein (ODAM) inhibits growth and migration of human melanoma cells and elicits PTEN elevation and inactivation of PI3K/AKT signaling.

BACKGROUND: The 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. METHODS: The 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. RESULTS: ODAM 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. CONCLUSIONS: The 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.

ODAM Expression Inhibits Human Breast Cancer Tumorigenesis.

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.

Percutaneous correction (humeroplasty) of humeral head defects (Hill-Sachs) associated with anterior shoulder instability: a cadaveric study.

PURPOSE: The goal of our study was to determine whether a bone tamp could be used to correct a Hill-Sachs lesion by a unique technique that we developed termed "humeroplasty." TYPE OF STUDY: In vitro cadaveric study. METHODS: We created reproducible Hill-Sachs lesions in 14 cadaveric humerii, which we then reduced with a curved bone tamp using our proposed technique. Paired t tests, with the significance set at P < .05, were then used to compare the prereduction and postreduction depths, widths, lengths, and volumes of the lesions. RESULTS: The average prereduction defect measurements were 8.9 mm deep, 16.3 mm wide, 24.1 mm long, and 1,755 mm3 in volume. The average postreduction defect measurements were 1.6 mm deep, 6.2 mm wide, 10.4 mm long, and 50.3 mm3 in volume. A statistically significant improvement (P < .001) was seen in all parameters. CONCLUSIONS: Our technique was able to consistently and significantly restore all measured parameters of the Hill-Sachs lesions using a curved bone tamp. This reduction to a "small" defect may reduce the higher rate of recurrence normally found with the surgical treatment of shoulder instability when "large" Hill-Sachs lesions are present. CLINICAL RELEVANCE: Humeroplasty potentially might reduce the higher rate of recurrence observed when the surgical treatment of shoulder instability involves the presence of large Hill-Sachs lesions.