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

<p>Abstract</p> <p>Background</p> <p>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?</p> <p>Methods</p> <p>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.</p> <p>Results</p> <p>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, β-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 (<it>PIK3R1</it>, <it>SOCS2</it>, <it>BMP7</it>, <it>CD44 </it>and <it>CD24</it>). 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.</p> <p>Conclusions</p> <p>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 β-catenin and CD44 upregulation, may characterize invasive cell populations in breast cancer.</p

Inflammation as a cardiovascular risk factor and pulse wave velocity as a marker of early-stage atherosclerosis in the Japanese population(日本人集団における心血管系危険因子としての炎症と早期アテローム性動脈硬化症の指標としての脈波伝播速度)

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Inflammation as a cardiovascular risk factor and pulse wave velocity as a marker of early-stage atherosclerosis in the Japanese population

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Inflammation as a cardiovascular risk factor and pulse wave velocity as a marker of early-stage atherosclerosis in the Japanese population

Inflammation and pulse wave velocity (PWV) are a potential risk factor and marker, respectively, for atherosclerosis in the primary prevention setting. Atherosclerosis is now generally accepted to be an inflammatory disorder of the arterial wall, and the high-sensitivity C-reactive protein (hs-CRP) level has been reported to be a strong predictor of cardiovascular events. High-sensitivity-CRP is associated with two factors related to inflammation: (1) the local production of CRP by atheromatous tissue or coronary artery smooth muscle cells and (2) adipose tissue as a potent source of inflammatory cytokines. Based on studies in North America and Europe, hs-CRP has been established as a cardiovascular risk factor and a cut-off value has been recommended. However, Japanese have lower hs-CRP values than their Western counterparts, partly because Japanese have a lower body mass index (BMI), which correlates positively to hs-CRP, and partly because lifestyle and genetic factors can affect hs-CRP values. Therefore, a cut-off value needs to be established by cohort studies for the Japanese population. Carotid-femoral PWV is most commonly measured by applanation tonometry, particularly in Europe, but this method is critically dependent upon the accurate placing of transducers over the arteries and is both time-consuming and complex. A novel device has been recently developed in Japan that measures brachial-ankle PWV (baPWV) using a volume-rendering method. Brachian-ankle PWV is a suitable screening method because of its technical simplicity and shorter measurement time. It is associated not only with conventional cardiovascular risk factors but also with new risk factors, such as inflammation, γ-glutamyltransferase, chronic kidney disease, and psychosocial factors. However, a suitable cut-off value has yet to be established