Bone marrow-derived cells are recruited by the melanoma tumor with endothelial cells contributing to tumor vasculature

• R. Bonfim-Silva ^[2] ; L. E. B. Souza ^[2] ; F. U. F. Melo ^[2] ; V. C. Oliveira ^[2] ; D. A. R. Magalhães ^[2] ; H. F. Oliveira ^[1] ; D. T. Covas ^[2] ; A. M. Fontes ^[2]
  1. [1] Universidade de São Paulo

     Universidade de São Paulo

     Brasil

     
  2. [2] National Institute of Science and Technology in Stem Cells and Cell Therapy, Brasil
• Localización: Clinical & translational oncology, ISSN 1699-048X, Vol. 19, Nº. 1 (January 2017), 2017, págs. 125-133
• Idioma: inglés
• Texto completo no disponible (Saber más ...)
• Resumen

  • Purpose 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.

    Conclusion 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.