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

The relation of polymorphisms in +874 region of IFN-Gama with occult HBV infection

Background and Objective: Occult hepatitis B infection is a form of hepatitis in which despite of absence of detectable HBsAg, HBV-DNA is present in peripheral blood of patients. The mechanisms which are responsible for progression of OBI yet to be clarified but some investigators believed that the genetics and immunological parameters may are different in resistant individuals and patients. Cytokine network system could be leading alteration in viral immune response. The aim of this study was to investigate the relation between polymorphisms +874 region of IFN-Gama with occult hepatitis B infection. Materials and Methods: In this study, the plasma samples of 3700 blood donors were tested for HBsAg and anti-HBs by ELISA. The HBsAg negative and anti-HBc positive samples were selected and screened for HBV-DNA by PCR. HBV-DNA positive samples assigned as occult hepatitis B infection cases and ARMS-PCR technique were performed to examine the present polymorphisms in +874 region of IFN-Gama genes of patients with occult hepatitis B infection. Results: 352 (9.51%) out of 3700 blood samples were negative for HBsAg and positive for anti-HBc antibody. HBV-DNA was detected in 57 (16.1%) of HBsAg negative and anti-HBc positive samples. Our results showed that there was not any significant difference between patients and control group in polymorphisms in +874 region of IFN-Gama genes. Conclusion: This study showed that there is not any significant difference between polymorphisms in +874 region with IFN-Gama occult hepatitis B infection