Nuclear beta-catenin and CD44 upregulation characterize invasive cell populations in non-aggressive MCF-7 breast cancer cells.

BACKGROUND: In breast cancer cells, the metastatic cell state is strongly correlated to epithelial-to-mesenchymal transition (EMT) and the CD44+/CD24- stem cell phenotype. However, the MCF-7 cell line, which has a luminal epithelial-like phenotype and lacks a CD44+/CD24- subpopulation, has rare cell populations with higher Matrigel invasive ability. Thus, what are the potentially important differences between invasive and non-invasive breast cancer cells, and are the differences related to EMT or CD44/CD24 expression? METHODS: Throughout the sequential selection process using Matrigel, we obtained MCF-7-14 cells of opposite migratory and invasive capabilities from MCF-7 cells. Comparative analysis of epithelial and mesenchymal marker expression was performed between parental MCF-7, selected MCF-7-14, and aggressive mesenchymal MDA-MB-231 cells. Furthermore, using microarray expression profiles of these cells, we selected differentially expressed genes for their invasive potential, and performed pathway and network analysis to identify a set of interesting genes, which were evaluated by RT-PCR, flow cytometry or function-blocking antibody treatment. RESULTS: MCF-7-14 cells had enhanced migratory and invasive ability compared with MCF-7 cells. Although MCF-7-14 cells, similar to MCF-7 cells, expressed E-cadherin but neither vimentin nor fibronectin, beta-catenin was expressed not only on the cell membrane but also in the nucleus. Furthermore, using gene expression profiles of MCF-7, MCF-7-14 and MDA-MB-231 cells, we demonstrated that MCF-7-14 cells have alterations in signaling pathways regulating cell migration and identified a set of genes (PIK3R1, SOCS2, BMP7, CD44 and CD24). Interestingly, MCF-7-14 and its invasive clone CL6 cells displayed increased CD44 expression and downregulated CD24 expression compared with MCF-7 cells. Anti-CD44 antibody treatment significantly decreased cell migration and invasion in both MCF-7-14 and MCF-7-14 CL6 cells as well as MDA-MB-231 cells. CONCLUSIONS: MCF-7-14 cells are a novel model for breast cancer metastasis without requiring constitutive EMT and are categorized as a "metastable phenotype", which can be distinguished from both epithelial and mesenchymal cells. The alterations and characteristics of MCF-7-14 cells, especially nuclear beta-catenin and CD44 upregulation, may characterize invasive cell populations in breast cancer.

A case of a large dermatofibrosarcoma protuberans successfully treated with radiofrequency ablation and transcatheter arterial embolization.

We present a large dermatofibrosarcoma protuberans on a 52 years-old woman's back that was successfully treated with transcatheter arterial embolization and radiofrequency ablation. The tumor developed on her back at the age of 14. Surgical treatment was not complete, and it relapsed at age 17 and again at age 24. The tumor enlarged to over 20x20x10 cm and flooded intermittently. The tumor cells with atypical nuclei were CD34 positive and proliferated in a storiform pattern. These findings were compatible with dermatofibrosarcoma protuberans. She was treated with blood transfusion for severe anemia. Two large feeding arteries were embolized, and the bottom of the tumor was treated with radiofrequency ablation. The tumor reduced in volume by more than 50%. It was then surgically removed and reconstructed with a free mesh skin graft. The combination pretreatment enabled radical resections of a large DFSP without severe complications.