Analyses of inhibitory effect of tumor angiogenesis, targeting the dynamism of bone marrow derived cells

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We have studied effect of NK4 through anti-angiogenesis so far. We realized that NK4 suppressed tumor growth more effective in spite of low concentration of NK4 in tumor by intra-peritoneal injection than by intra-tumoral injection. We evaluated the recruitment of cells from bone marrow to xenograft tumor after transforming of NK4 adenovirus.Method : Bone marrow transplantation was established below. The C57BL6 mice were exposed by lethal irradiation of 12Gy and transplanted hematopoietic stem cells from GFP mice. By this procedure, about 80% chimera mice can be obtained 2 weeks after bone marrow transplantation. Next, the chimera mice were inoculated LLC tumor infected by NK4 adenovirus (AdNK4)or Null adenovirus (AdNull). The tumor implanted in mice were measured in length and resected on day14 after inoculation and evaluated bone marrow derived cell and cells structured vessels dyed with zennon TM Tricolor Labeling Kit (Molecular probe) by laser scanning microscopyResult : In vitro t … More here is no difference in growth of tumor cells infected with between NK4 adenovirus and Null adenovirus however, in vivo AdNK4 infected tumor were suppressed significantly in tumor growth. Though there are considerable amount of GFP positive cells infiltrated in tumor, most GFP positive cells did not merge with cells structured vessels. In resected tumor of NK4 groups, both tumor vessels and bone marrow derived cells decreased significantly. Many bone marrow derived cells were dyed with hematocyte markers (CD45 positive cells / GFP positive cells AdNK4 71.3%, AdNull 66.0% ). Interestingly, VEGF positive bone marrow derived cells decreaced considerably in tumor infected with AdNK4 compared to tumor infected with AdNull (GFP, VEGF double positive / total GFP positive cells: 36.3%, 8.2% respectively). The origin and differentiation of VEGF positive bone marrow derived cells has not unknown yet.Conclusion : In this study, we could not find direct relation between anti-angiogenic effect and bone marrow derived cells, however, bone marrow derived cells decreased in tumor infected with NK4., These cells possibly have some effect on tumor angiogenesis in the paracrine manner. Further examination on the association among angiogenesis and bone marrow derived cells in the tumor suppressed by NK4 is needed. Less