Zhu et al. Journal of Experimental & Clinical Cancer Research 2012, 31:31 http://www.jeccr.com/content/31/1/31 Page 6 of 7 Figure 4 Activation of Akt protein involved in BLyS-enhanced cell migration. (A) Decreased number of migrated MDA-MB-435 cells was examined when the cells were treated with API-1 (10 μM) and SB 202190 (5 μM) for 8 h (original magnification 200 ×). Data were means of triplicate samples with ± SD; vs 2% FBS, **, P < 0.01; vs BLyS (10 ng/ml), ###, P < 0.001. (B) Phosphorylation of Akt and p38 MAPK proteins in MDA-MB-435 cells by Western Blotting analysis. (C) MDA-MB-435 cells were challenged with API-1 and SB 202190 for 4 h. API-1 inhibited the BLyS-induced (10 ng/ml) phosphorylation of Akt. breast cancer cell migration in response to BLyS in vitro. BlyS, an immunopotentiator, might be a potential therapeutic target in breast cancer treatment base on this study, but care should be taken for using immuno- potentiator in cancer treatment. Cancer tissues consist of large amounts of mesenchymal cells including fibro- blasts, endothelial cells, adipocytes as well as inflamma- tory cells. As we know, inflammatory cells are a major source of BLyS, suggesting that BLyS may act as a con- nection between inflammatory cells and cancer cells. Furthermore, growing evidences show that cancer can evolve from chronic inflammation [16]. Inflammation often accompanies cancer and recruits inflammatory cells which release plenty of inflammatory factors [17]. In addition, cancer-associated fibroblasts mediate can- cer-enhancing inflammation [18]. Despite the relation- ship between inflammation and cancer is still poorly understood, it is believed that inflammatory cells are not the “street sweeper” in cancer tissues all along, but may trigger cancer progression [19]. Many other processes, such as EMT, are involved in the transition from inflam- mation to cancer [20]. It is prospected that an advanced breast cancer treatment could be developed if this field is much deeply explored. Previous study reported that NF-kappa B played a key role in the transition from inflammation to cancer [21]. Cancer with NF-kappa B activity usually shows increased resistance to chemotherapy [22]. Furthermore, NF-kappa B is required for the expressions of many inflammatory genes [23]. Curcumin inhibited BLyS expression by decreasing the nuclear translocation of p65 in B lympho- cyte cell lines [10]. Regarding HIF-1a, its protein level is extremely low in normoxic conditions. HIF-1a protein accumulates under hypoxia and regulates the target genes [8]. Interestingly, NF-kappa B also activates angio- genesis encoding genes HIF-1a and VEGF [24,25]. Mobi- lity of cancer cells and cytokines productions are altered by hypoxia. All of these alterations will finally lead to angiogenesis, matrix degradation and metastasis in can- cer. Cancer cells adapt to hypoxia for survival [26]. It is reported that BLyS suppresses the progression of several kinds of tumors and plays an important role in the development of immune system diseases [27]. How- ever, our results showed an enhanced migratory in response to BLyS. Several reports support the critical roles of Akt and p38 MAPK in cancer cell survival, migration, apoptosis and anti-apoptosis [28,29]. Previous research indicated that BLyS led to rapid phosphoryla- tions of Akt in B cells [30]. Our studies suggested that phosphorylations of Akt were essential for BLyS- enhanced cell migration in vitro. Conclusion In conclusion, the results found that BLyS caused the enhanced migration of human breast cancer cells, while BLyS was up-regulated by hypoxia. However, further studies are required to confirm the mechanisms of BLyS action and reveal the relationship between inflammation and breast cancer progression. Acknowledgements This work was supported by the Standardized Platform Construction and Scientific Application in New Technologies for New Drug Screening (No.2009ZX09302-002), the Study of Saponin Monomer of Dwarf Lilyturf Tuber (DT-13): A new Natural Anti-metastatic Drug Candidate (No.2009ZX09103-308) and the Research on Anti-tumor metastasis effectof YS-1 (No.81071841)