This was further proved by CXCR4 antagonist AMD3100, which significantly reduced MFE and the expression of BCSC markers in secondary mammosphere www.selleckchem.com/products/AZD1152-HQPA.html cells. Collectively, these data indicated that the specific interactions of SDF-1 with their receptor CXCR4 that expressed on mammosphere cells are likely to occur in tumor-stromal niches, and these interactions may be responsible for the proliferation of CD44+CD24- cells. The proliferation of mammosphere cells was observed to be promoted by being cocultured with CAFs, suggesting that SDF-1/CXCR4 signaling is involved in the cell proliferation of these cocultured mammosphere cells. CXCR4 and SDF-1 are candidate

factors that involved in the cross-talk of the tumor-niche interaction of CD44+CD24- cells. Because the increase in the proliferation of cocultured mammosphere cells induced by SDF-1 was completely inhibited by AMD3100, therapeutic strategies that target SDF-1/CXCR4 may be beneficial to breast cancer patients. So, new strategies need

to take into account the role of the niches that can have a critical role in modulating BCSCs and response to therapeutic agents. It should be noted that this study had only examined the interaction of stromal fibroblasts and CD44+CD24- cells in two dimensions, and how they interact with each other in three-dimensional culture remains to be further studied. Acknowledgements The authors express great gratitude to the surgeon staff of Xinhua Hospital (Shanghai Jiao Tong buy ITF2357 University School of Medicine, Shanghai, Selleckchem Caspase inhibitor China) for their kind assistance. Electronic supplementary material Additional file 1: Additional samples analyzed with FACS as described in legend for Figure 3. The data provided represent the other two tests analyzed with FACS as described in legend for Figure 3. (JPEG 68 KB) Additional file 2: Additional samples analyzed with FACS as described in legend for Figure 6. The data provided represent the other two tests analyzed with FACS as described in legend for Figure 6. (JPEG 65 KB) References

1. Parkin DM, Bray F, Ferlay J, Pisani P: Estimating the world cancer burden: Globocan 2000. Int J Cancer 2001, 94:153–156.PubMedCrossRef 2. Zhang M, Rosen JM: Stem cells in the etiology and treatment of cancer. Curr Opin Genet Dev 2006, 16:60–64.PubMedCrossRef 3. Al-Hajj C1GALT1 M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF: Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci USA 2003, 100:3983–3988.PubMedCrossRef 4. Bonnet D, Dick JE: Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med 1997, 3:730–737.PubMedCrossRef 5. Singh SK, Hawkins C, Clarke ID, Squire JA, Bayani J, Hide T, Henkelman RM, Cusimano MD, Dirks PB: Identification of human brain tumour initiating cells. Nature 2004, 432:396–401.PubMedCrossRef 6.