Immunohistochemically, cadherin-11, N-cadherin, and beta-catenin were expressed at the cell surface of fetal osteoblasts, whereas in osteosarcoma cells, they were expressed only focally or weakly in the cytoplasm.
In our survival analysis, beta-catenin deregulation conferred a hazard ratio of 1.05, indicating that beta-catenin accumulation does not appear to be of prognostic value for osteosarcoma patients.
These data indicate that the cytoplasmic and/or nuclear staining of beta-catenin is a biological marker of metastatic potential of osteosarcoma to the lung.
Expression rates driven by osteoblast- specific fragments from the collagen1A1-promoter, the human Osteocalcin-promoter, the bone-sialoprotein promoter and the beta-catenin promoter depending on vitamin supplementation were analysed in five OS cell lines, in normal lung fibroblasts and in a non-osteoblastic prostate cancer cell line (LNCaP) by dual luciferase assays.
In vitro, WIF1 suppressed beta-catenin levels in human osteosarcoma cell lines, induced differentiation of human and mouse primary osteoblasts, and suppressed the growth of mouse and human osteosarcoma cell lines.
Overexpression of the wild-type β-catenin plasmid in osteosarcoma cells resulted in enhanced cell invasiveness but this effect was significantly overcome by curcumin.
The clinical, demographic, anatomic and pathological factors including a detailed analysis of the immunohistochemical expression of cadherin, β-catenin and APC were retrospectively examined in 97 patients with osteosarcoma of the extremities (metastatic and non-metastatic at diagnosis), treated with surgery and/or chemotherapy from 1985 to 2000.
Altogether, these data provide evidence that the repression of syndecan-2 by Wnt/β-catenin/TCF signaling contributes to the resistance of osteosarcoma cells to doxorubicin and suggest that TCF inhibition may represent a novel therapeutic strategy in osteosarcoma.
In conclusion, we demonstrate that TWIST decreases osteosarcoma cell survival against cisplatin by decreasing the soluble β-catenin level through a PI3K-dependent manner.
Consistently, the expression level of β-catenin protein correlated with the invasiveness of OS, as evidenced by more intensive β-catenin immunoreactivity in higher grade OS samples.
Using immunohistochemical staining and western blot analysis, the degree of the expression of BAMBI and β-catenin was significantly higher in osteosarcoma specimens compared with normal tissues.
In line with deletions of the latter two genes, high beta-catenin protein expression has previously been reported in osteoblastoma and aberrations affecting the Wnt/beta-catenin pathway have been found in other bone lesions, including osteoma and osteosarcoma.
In conclusion, the present study suggested that NOB1 depletion may inhibit osteosarcoma development by increasing E-cadherin and β-catenin expression and, for the first time, indicated the potential of NOB1 as a target in osteosarcoma treatment.
β-catenin protein expression was, however, detected in the membrane and cytoplasm of 69.6% (32/46) of the osteosarcomas. c-myc protein expression was detected in only 47.8% (22/46) and cyclin D1 protein expression in 52.2% (24/46) of osteosarcoma samples.
The results showed that the expression of CXCR4 and β-catenin mRNA and protein was significantly higher in OS tissues compared to the surrounding non-neoplastic tissues.
The results of subsequent western blot and reverse transcription‑quantitative polymerase chain reaction analyses revealed that the protein levels of β‑catenin and cyclin D1 were markedly upregulated in the fluorescence‑activated cell sorted osteosarcoma SP cells.
We conclude that CD151 knockdown inhibits the expression of MMP9 through the GSK-3β/β‑catenin pathway and also inhibits OS migration and invasion in vitro and metastasis in vivo in highly metastatic OS.
We also investigated changes in expression, phosphorylation and co-transcriptional activity of β-catenin in osteosarcoma cells following GSK-3β inhibition.
In addition, 2-ME treatment regulates downstream Wnt signaling, increasing the cytoplasmic levels of β-catenin, and blocking β-catenin-mediated Wnt activation in osteosarcoma cells.