MCP-1/CCL2 plays an important role in the initiation and progression of cancer. Since tumor cells produce MCP-1, they are considered to be the main source of this chemokine. Here, we examined whether MCP-1 produced by non-tumor cells affects the growth and lung metastasis of 4T1 breast cancer cells by transplanting them into the mammary pad of WT or MCP-1−/− mice. Primary tumors at the injected site grew similarly in both mice; however, lung metastases were markedly reduced in MCP-1−/− mice, with significantly longer mouse survival. High levels of MCP-1 mRNA were detected in tumors growing in WT, but not MCP-1−/− mice. Serum MCP-1 levels were increased in tumor-bearing WT, but not MCP-1−/− mice. Transplantation of MCP-1−/− bone marrow cells into WT mice did not alter the incidence of lung metastasis, whereas transplantation of WT bone marrow cells into MCP-1−/− mice increased lung metastasis. The primary tumors of MCP-1−/− mice consistently developed necrosis earlier than those of WT mice and showed decreased infiltration by macrophages and reduced angiogenesis. Interestingly, 4T1 cells that metastasized to the lung constitutively expressed elevated levels of MCP-1, and intravenous injection of 4T1 cells producing a high level of MCP-1 resulted in increased tumor foci in the lung of WT and MCP-1−/− mice. Thus, stromal cell-derived MCP-1 in the primary tumors promotes lung metastasis of 4T1 cells, but tumor cell-derived MCP-1 can also contribute once tumor cells enter the circulation. A greater understanding of the source and role of this chemokine may lead to novel strategies for cancer treatment.

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Bovine torovirus (BToV) is recognized as an enteric pathogen of calves, but its etiological role in diarrhea and epidemiological characterization in adult cows remain unclear. In 2007-2008, three outbreaks of epidemic diarrhea occurred in adult cows at three dairy farms in Niigata Prefecture, Japan. BToV was the only enteric pathogen detected in these outbreaks, as determined by electron microscopy, reverse transcription-PCR, bacteria and parasite tests of fecal samples, and antibody tests with paired sera. The epidemiological features of the three outbreaks were similar to those of bovine coronavirus infection, except for the absence of bloody diarrhea, with diarrhea spreading among most adult cows, but not in calves, within several days and diarrhea lasting for 3-5 days with anorexia. Decreased milk production and mild respiratory symptoms were also observed in two of the outbreaks. Nucleotide sequence analysis of the BToV nucleocapsid, spike, and hemagglutinin-esterase (HE) genes revealed a close relatedness among the detected BToV strains from each outbreak and those of Japanese BToV strain Aichi/2004. Furthermore, we isolated a BToV strain, designated Niigata (TC), from a fecal sample using a human rectal tumor cell line. Sequence analysis of this isolate and Aichi/2004 indicated that both strains have truncated HE genes with deletions in the 3' region that occurred through cell culture-adaptation. The short projections that are believed to be formed by the HE protein on virus particles were not observed in these cultured strains by electron microscopy. Taken together, these results suggest that BToV causes epidemic diarrhea in adult cows and should be included in the differential diagnosis of diarrhea in adult cows. In addition, our findings indicate that the HE protein of BToV may not be necessary for viral replication.

Background -Silica-induced pulmonary inflammation and fibrosis in animals provides a good model for chronic pulmonary inflammation and fibrosis. Although lymphocytes are implicated in the pathogenesis of pulmonary fibrosis, experimental models using silica-treated athymic nude mice have not been successful in showing the fibrogenic mechanism regulated by T cells. The aim of this study was to re-evaluate the role of T lymphocytes in the development of silicosis by comparing the response to silica administration of nude athymic mutants with that of euthymic animals. Methods -Suspensions of silica particles were transnasally administered to nude athymic mice (BalbIc nu/nu) as well as to their euthymic littermates (Balb/c nu/+). The degree of pulmonary inflammation and fibrosis was assessed on days 14, 28, and 56 based upon histological observation, analysis of collagen deposition in the lungs, and analysis of the cellular constituent, protein, and phospholipid content in the bronchoalveolar lavage fluid. Results -Histologically, athymic mice developed less severe interstitial pneumonitis than euthymic mice. In euthymic mice the lung hydroxyproline content increased with time after silica administration from 6.48 (0.38) gg hydroxyproline/mg dry lung weight on day 0 to 8.87 (0.41) ftg/mg on day 56. A gradual increase in lung hydroxyproline content was also observed in athymic mice but the increase was significantly smaller than in euthymic mice (6.63 (0.43)