Metastatic progression depends on genetic alterations intrinsic to cancer cells as well as the inflammatory microenvironment of advanced tumors 1,2 . To understand how cancer cells affect the inflammatory microenvironment, we conducted a biochemical screen for macrophage activating factors secreted by metastatic carcinomas. Amongst the cell lines screened, Lewis lung carcinoma (LLC) 3 were the most potent macrophage activators leading to production of IL-6 and TNF-α through activation of the Toll-like receptor family members 4 TLR2 and TLR6. Both TNF-α and TLR2 were found to be required for LLC metastasis. Biochemical purification of LLC conditional medium (LCM) led to identification of the extracellular matrix proteoglycan versican, which is upregulated in many human tumors including lung cancer 5,6 , as a macrophage activator that acts via TLR2 and its co-receptors TLR6 and CD14. By activating TLR2:TLR6 complexes and inducing TNF-α secretion by myeloid cells, versican strongly enhances LLC metastatic growth. These results explain how advanced cancer cells usurp components of the host innate immune system, including bone marrow-derived myeloid progenitors 7 , to generate an inflammatory microenvironment hospitable for metastatic growth.Distant site metastases are the leading cause of cancer-associated mortality and depend on genetic and/or epigenetic alterations that are intrinsic to cancer cells or extrinsic factors provided by the tumor microenvironment 1 . For instance, cytokines produced by inflammatory cells can enhance metastatogenesis by repressing the metastasis suppressor maspin within primary prostate carcinoma cells 8 . Furthermore, tumor progression and metastasis positively correlate with presence of infiltrates containing myeloid and lymphoid cells 2,9 . It was shown that certain carcinomas secrete factors that upregulate fibronectin and recruit vascular endothelial growth factor receptor 1 (VEGFR1)-positive hematopoetic progenitors to sites of Correspondence and requests for materials should be addressed to M.K. future metastatic growth, termed the pre-metastatic niche 7 . To examine whether cancer cells secrete factors that directly activate myeloid cells to produce tumor promoting cytokines 10 , we collected serum free conditioned medium (CM) from different cancer cell lines, derived mainly from C57BL6 mice, and applied it to bone marrow (BM)-derived macrophages (BMDM), which were assayed for production of IL-1β, IL-6 and TNF-α. The screen included 1C1C7 and TrampC1, which are liver and prostate cancer cell lines, respectively, with little or no metastatic activity, and two metastatic breast and lung carcinomas, 4T1 and LLC, respectively. CM from metastatic cells, especially LLC, induced higher amounts of IL-6 and TNF-α secretion than CM from non-metastatic cells (Fig. 1A). IL-1β secretion was undetectable and the CM did not contain IL-6 or TNF-α (data not shown). LLC-CM (LCM) also induced expression of Il1β, Il6 and Tnfα mRNAs, whereas serum free medium (SFM) and NIH3T3 CM were inacti...

The vanadium redox flow battery, which was first suggested by Skyllas -Kazacos and co-workers in 1985, is an electrochemical storage system which allows energy to be stored in two solutions containing different redox couples. Unlike commercially available batteries, all vanadium redox flow batteries have unique configurations, determined by the size of the electrolyte tanks. This technology has been proven to be an economically attractive and low-maintenance solution, with significant benefits over the other types of batteries. Moreover, the soaring demand for large-scale energy storage has, in turn, increased demands for unlimited capacity, design flexibility, and good safety systems. This work reviews and discusses the progress on electrodes their reaction mechanisms as key components of the vanadium redox flow battery over the past 30 years. In terms of future outlook, we also provide practical guidelines for the further development of self-sustaining electrodes for vanadium redox flow batteries as an attractive energy storage system.