title: Bone marrow-derived cells are recruited by the melanoma tumor with endothelial cells contributing to tumor vasculature.
abstract: OBJECTIVE
  Tumor expansion is dependent on neovascularization, a process that requires sustained new vessel formation. Although the critical role of angiogenesis by endothelial sprouting in this process, controversy still prevails on whether angiogenesis involving bone marrow-derived endothelial cells, does contribute to this process. This study aims to evaluate the recruitment of bone marrow-derived cells by the melanoma tumor, including endothelial cells, and if they contribute to angiogenesis.
  
  
  METHODS
  A chimeric mouse model of GFP bone marrow was used to induce melanoma tumors derived from murine B16-F10 cell line. These tumors were evaluated for the presence of myeloid cells (CD11b), T lymphocytes (CD3, CD4 and CD8) and endothelial cells (VEGFR2 and CD31) derived from bone marrow.
  
  
  RESULTS
  Mice transplanted with GFP+ cells showed significant bone marrow chimerism (90.9 ± 0.87 %) when compared to the GFP transgenic mice (90.66 ± 2.1 %, p = 0.83) demonstrating successful engraftment of donor bone marrow stem/progenitor cells. Analysis of the murine melanoma tumor showed the presence of donor cells in the tumors (3.5 ± 1.7 %) and interestingly, these cells represent endothelial cells (CD31+ cells; 11.5 ± 6.85 %) and myeloid cells (CD11b+ cells; 80 ± 21 %), but also tumor-infiltrating lymphocytes (CD8+ T cells, 13.31 ± 0.2 %; CD4+ T-cells, 2.1 ± 1.2 %). Examination of the tumor endothelium by confocal microscopy suggests the presence of donor CD31+/GFP+ cells in the wall of some blood vessels.
  
  
  CONCLUSIONS
  This study demonstrates that bone marrow-derived cells are recruited by the murine melanoma tumor, with myeloid cells and CD4 and CD8 T lymphocytes migrating as antitumor immune response, and endothelial cells participating of the tumor blood vessels formation.
authors.affiliation: National Institute of Science and Technology in Stem Cells and Cell Therapy, Avenida Tenente Catão Roxo, 2501, Monte Alegre, Ribeirão Preto, São Paulo, 14051-140, Brazil. bonfim.ricardo@gmail.com.|Department of Genetics, Medical School of Ribeirão Preto, University of São Paulo, Avenida Bandeirantes, 3900, Vila Monte Alegre, Ribeirão Preto, São Paulo, 14049-900, Brazil. bonfim.ricardo@gmail.com.
authors.forename: R
authors.initials: R
authors.lastname: Bonfim-Silva
authors.affiliation: National Institute of Science and Technology in Stem Cells and Cell Therapy, Avenida Tenente Catão Roxo, 2501, Monte Alegre, Ribeirão Preto, São Paulo, 14051-140, Brazil.|Department of Clinical Medicine, Medical School of Ribeirão Preto, University of São Paulo, Avenida Bandeirantes, 3900, Monte Alegre, Ribeirão Preto, São Paulo, 14048-900, Brazil.
authors.forename: L E B
authors.initials: LE
authors.lastname: Souza
authors.affiliation: National Institute of Science and Technology in Stem Cells and Cell Therapy, Avenida Tenente Catão Roxo, 2501, Monte Alegre, Ribeirão Preto, São Paulo, 14051-140, Brazil.|Department of Clinical Medicine, Medical School of Ribeirão Preto, University of São Paulo, Avenida Bandeirantes, 3900, Monte Alegre, Ribeirão Preto, São Paulo, 14048-900, Brazil.
authors.forename: F U F
authors.initials: FU
authors.lastname: Melo
authors.affiliation: National Institute of Science and Technology in Stem Cells and Cell Therapy, Avenida Tenente Catão Roxo, 2501, Monte Alegre, Ribeirão Preto, São Paulo, 14051-140, Brazil.
authors.forename: V C
authors.initials: VC
authors.lastname: Oliveira
authors.affiliation: National Institute of Science and Technology in Stem Cells and Cell Therapy, Avenida Tenente Catão Roxo, 2501, Monte Alegre, Ribeirão Preto, São Paulo, 14051-140, Brazil.
authors.forename: D A R
authors.initials: DA
authors.lastname: Magalhães
authors.affiliation: Department of Clinical Medicine, Medical School of Ribeirão Preto, University of São Paulo, Avenida Bandeirantes, 3900, Monte Alegre, Ribeirão Preto, São Paulo, 14048-900, Brazil.
authors.forename: H F
authors.initials: HF
authors.lastname: Oliveira
authors.affiliation: National Institute of Science and Technology in Stem Cells and Cell Therapy, Avenida Tenente Catão Roxo, 2501, Monte Alegre, Ribeirão Preto, São Paulo, 14051-140, Brazil.|Department of Clinical Medicine, Medical School of Ribeirão Preto, University of São Paulo, Avenida Bandeirantes, 3900, Monte Alegre, Ribeirão Preto, São Paulo, 14048-900, Brazil.
authors.forename: D T
authors.initials: DT
authors.lastname: Covas
authors.affiliation: National Institute of Science and Technology in Stem Cells and Cell Therapy, Avenida Tenente Catão Roxo, 2501, Monte Alegre, Ribeirão Preto, São Paulo, 14051-140, Brazil.|Department of Genetics, Medical School of Ribeirão Preto, University of São Paulo, Avenida Bandeirantes, 3900, Vila Monte Alegre, Ribeirão Preto, São Paulo, 14049-900, Brazil.
authors.forename: A M
authors.initials: AM
authors.lastname: Fontes
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology*; D016026:Bone Marrow Transplantation; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating / Q000473:pathology*; D008546:Melanoma, Experimental / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009389:Neovascularization, Pathologic
chemical_list: C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins
keywords: Angiogenesis; Bone marrow transplantation; Cell migration; Endothelial cells; Melanoma stroma