Mesenchymal Stem Cells Promote Mammosphere Formation and Decrease E-Cadherin in Normal and Malignant Breast Cells

Normal and malignant breast tissue contains a rare population of multi-potent cells with the capacity to self-renew, referred to as stem cells, or tumor initiating cells (TIC). These cells can be enriched by growth as "mammospheres" in three-dimensional cultures.We tested the hypothesis that human bone-marrow derived mesenchymal stem cells (MSC), which are known to support tumor growth and metastasis, increase mammosphere formation.We found that MSC increased human mammary epithelial cell (HMEC) mammosphere formation in a dose-dependent manner. A similar increase in sphere formation was seen in human inflammatory (SUM149) and non-inflammatory breast cancer cell lines (MCF-7) but not in primary inflammatory breast cancer cells (MDA-IBC-3). We determined that increased mammosphere formation can be mediated by secreted factors as MSC conditioned media from MSC spheroids significantly increased HMEC, MCF-7 and SUM149 mammosphere formation by 6.4 to 21-fold. Mammospheres grown in MSC conditioned media had lower levels of the cell adhesion protein, E-cadherin, and increased expression of N-cadherin in SUM149 and HMEC cells, characteristic of a pro-invasive mesenchymal phenotype. Co-injection with MSC in vivo resulted in a reduced latency time to develop detectable MCF-7 and MDA-IBC-3 tumors and increased the growth of MDA-IBC-3 tumors. Furthermore, E-cadherin expression was decreased in MDA-IBC-3 xenografts with co-injection of MSC.MSC increase the efficiency of primary mammosphere formation in normal and malignant breast cells and decrease E-cadherin expression, a biologic event associated with breast cancer progression and resistance to therapy

An experimental and analytical investigation of reinforced concrete beam-column joints strengthened with a range of CFRP schemes applied only to the beam

This paper investigates the experimental and analytical behaviour of beam-column joints that are subjected to a combination of torque, flexural and direct shear forces, where different Carbon Fibre Polymer (CFRP) strengthening wraps have been applied only to the beam. These wrapping schemes have previously been determined by the research community as an effective method of enhancing the torsional capacities of simply supported reinforced concrete beams. In this investigation, four 3/4-scale exterior beam-column joints were subjected to combined monotonic loading; three different beam wrapping schemes were employed to strengthen the beam region of the joint. The paper suggests a series of rational formulae, based on the space truss mechanism, which can be used to evaluate the joint shear demand of the beams wrapped in these various ways. Further, an iterative model, based on the average stress-strain method, has been introduced to predict joint strength. The proposed analytical approaches show good agreement with the experimental results. The experimental outcomes along with the adopted analytical methods reflect the consistent influence of the wrapping ratio, the interaction between the combined forces, the concrete strut capacity and the fibre orientation on the joint forces, the failure mode and the distortion levels. A large rise in the strut force resulting from shear stresses generated from this combination of forces is demonstrated and leads to a sudden-brittle failure. Likewise, increases in the beams’ main steel rebar strains are identified at the column face, again influenced by the load interactions and the wrapping systems used