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Title: Intravenous administration of bone marrow-derived multipotent mesenchymal stromal cells enhances the recruitment of CD11b{sup +} myeloid cells to the lungs and facilitates B16-F10 melanoma colonization

Abstract

The discovery that the regenerative properties of bone marrow multipotent mesenchymal stromal cells (BM-MSCs) could collaterally favor neoplastic progression has led to a great interest in the function of these cells in tumors. However, the effect of BM-MSCs on colonization, a rate-limiting step of the metastatic cascade, is unknown. In this study, we investigated the effect of BM-MSCs on metastatic outgrowth of B16-F10 melanoma cells. In in vitro experiments, direct co-culture assays demonstrated that BM-MSCs stimulated the proliferation of B16-F10 cells in a dose-dependent manner. For in vivo experiments, luciferase-expressing B16-F10 cells were injected through tail vein and mice were subsequently treated with four systemic injections of BM-MSCs. In vivo bioluminescent imaging during 16 days demonstrated that BM-MSCs enhanced the colonization of lungs by B16-F10 cells, which correlated with a 2-fold increase in the number of metastatic foci. Flow cytometry analysis of lungs demonstrated that although mice harboring B16-F10 metastases displayed more endothelial cells, CD4 T and CD8 T lymphocytes in the lungs in comparison to metastases-free mice, BM-MSCs did not alter the number of these cells. Interestingly, BM-MSCs inoculation resulted in a 2-fold increase in the number of CD11b{sup +} myeloid cells in the lungs of melanoma-bearing animals, amore » cell population previously described to organize “premetastatic niches” in experimental models. These findings indicate that BM-MSCs provide support to B16-F10 cells to overcome the constraints that limit metastatic outgrowth and that these effects might involve the interplay between BM-MSCs, CD11b{sup +} myeloid cells and tumor cells. - Highlights: • BM-MSCs enhanced B16-F10 proliferation in a dose-dependent manner in vitro. • BM-MSCs facilitated lung colonization by B16-F10 melanoma cells. • BM-MSCs administration did not alter the number of endothelial cells and T lymphocytes in the lungs. • BM-MSCs enhanced the recruitment of CD11b{sup +} myeloid cells during tumor colonization.« less

Authors:
 [1];  [2];  [3];  [4];  [1];  [2];  [5]
  1. Department of Clinical Medicine, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP (Brazil)
  2. (Brazil)
  3. Department of Medicine – Nephrology, Laboratory of Clinical and Experimental Immunology, Federal University of São Paulo, São Paulo, SP (Brazil)
  4. Department of Biochemistry and Immunology, Basic and Applied Immunology Program, School of Medicine of Ribeirão Preto, University of São Paulo (Brazil)
  5. Department of Genetics, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP (Brazil)
Publication Date:
OSTI Identifier:
22648593
Resource Type:
Journal Article
Journal Name:
Experimental Cell Research
Additional Journal Information:
Journal Volume: 345; Journal Issue: 2; Other Information: Copyright (c) 2015 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0014-4827
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; BEARINGS; BIOMEDICAL RADIOGRAPHY; BONE MARROW; BORON 16; DOSES; HARBORS; IN VITRO; IN VIVO; INJECTION; INOCULATION; LIMITING VALUES; LUCIFERASE; LUNGS; LYMPHOCYTES; MELANOMAS; METASTASES; MICE; PROLIFERATION; SKELETON; SUPPORTS; TUMOR CELLS; VEINS

Citation Formats

Souza, Lucas E.B., E-mail: lucasebsouza@usp.br, Hemotherapy Center of Ribeirão Preto, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Almeida, Danilo C., E-mail: gudaalmeida@gmail.com, Yaochite, Juliana N.U., E-mail: ueda.juliana@gmail.com, Covas, Dimas T., E-mail: dimas@fmrp.usp.br, Hemotherapy Center of Ribeirão Preto, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, and Fontes, Aparecida M., E-mail: aparecidamfontes@usp.br. Intravenous administration of bone marrow-derived multipotent mesenchymal stromal cells enhances the recruitment of CD11b{sup +} myeloid cells to the lungs and facilitates B16-F10 melanoma colonization. United States: N. p., 2016. Web. doi:10.1016/J.YEXCR.2015.05.021.
Souza, Lucas E.B., E-mail: lucasebsouza@usp.br, Hemotherapy Center of Ribeirão Preto, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Almeida, Danilo C., E-mail: gudaalmeida@gmail.com, Yaochite, Juliana N.U., E-mail: ueda.juliana@gmail.com, Covas, Dimas T., E-mail: dimas@fmrp.usp.br, Hemotherapy Center of Ribeirão Preto, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, & Fontes, Aparecida M., E-mail: aparecidamfontes@usp.br. Intravenous administration of bone marrow-derived multipotent mesenchymal stromal cells enhances the recruitment of CD11b{sup +} myeloid cells to the lungs and facilitates B16-F10 melanoma colonization. United States. doi:10.1016/J.YEXCR.2015.05.021.
Souza, Lucas E.B., E-mail: lucasebsouza@usp.br, Hemotherapy Center of Ribeirão Preto, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Almeida, Danilo C., E-mail: gudaalmeida@gmail.com, Yaochite, Juliana N.U., E-mail: ueda.juliana@gmail.com, Covas, Dimas T., E-mail: dimas@fmrp.usp.br, Hemotherapy Center of Ribeirão Preto, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, and Fontes, Aparecida M., E-mail: aparecidamfontes@usp.br. Fri . "Intravenous administration of bone marrow-derived multipotent mesenchymal stromal cells enhances the recruitment of CD11b{sup +} myeloid cells to the lungs and facilitates B16-F10 melanoma colonization". United States. doi:10.1016/J.YEXCR.2015.05.021.
@article{osti_22648593,
title = {Intravenous administration of bone marrow-derived multipotent mesenchymal stromal cells enhances the recruitment of CD11b{sup +} myeloid cells to the lungs and facilitates B16-F10 melanoma colonization},
author = {Souza, Lucas E.B., E-mail: lucasebsouza@usp.br and Hemotherapy Center of Ribeirão Preto, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP and Almeida, Danilo C., E-mail: gudaalmeida@gmail.com and Yaochite, Juliana N.U., E-mail: ueda.juliana@gmail.com and Covas, Dimas T., E-mail: dimas@fmrp.usp.br and Hemotherapy Center of Ribeirão Preto, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP and Fontes, Aparecida M., E-mail: aparecidamfontes@usp.br},
abstractNote = {The discovery that the regenerative properties of bone marrow multipotent mesenchymal stromal cells (BM-MSCs) could collaterally favor neoplastic progression has led to a great interest in the function of these cells in tumors. However, the effect of BM-MSCs on colonization, a rate-limiting step of the metastatic cascade, is unknown. In this study, we investigated the effect of BM-MSCs on metastatic outgrowth of B16-F10 melanoma cells. In in vitro experiments, direct co-culture assays demonstrated that BM-MSCs stimulated the proliferation of B16-F10 cells in a dose-dependent manner. For in vivo experiments, luciferase-expressing B16-F10 cells were injected through tail vein and mice were subsequently treated with four systemic injections of BM-MSCs. In vivo bioluminescent imaging during 16 days demonstrated that BM-MSCs enhanced the colonization of lungs by B16-F10 cells, which correlated with a 2-fold increase in the number of metastatic foci. Flow cytometry analysis of lungs demonstrated that although mice harboring B16-F10 metastases displayed more endothelial cells, CD4 T and CD8 T lymphocytes in the lungs in comparison to metastases-free mice, BM-MSCs did not alter the number of these cells. Interestingly, BM-MSCs inoculation resulted in a 2-fold increase in the number of CD11b{sup +} myeloid cells in the lungs of melanoma-bearing animals, a cell population previously described to organize “premetastatic niches” in experimental models. These findings indicate that BM-MSCs provide support to B16-F10 cells to overcome the constraints that limit metastatic outgrowth and that these effects might involve the interplay between BM-MSCs, CD11b{sup +} myeloid cells and tumor cells. - Highlights: • BM-MSCs enhanced B16-F10 proliferation in a dose-dependent manner in vitro. • BM-MSCs facilitated lung colonization by B16-F10 melanoma cells. • BM-MSCs administration did not alter the number of endothelial cells and T lymphocytes in the lungs. • BM-MSCs enhanced the recruitment of CD11b{sup +} myeloid cells during tumor colonization.},
doi = {10.1016/J.YEXCR.2015.05.021},
journal = {Experimental Cell Research},
issn = {0014-4827},
number = 2,
volume = 345,
place = {United States},
year = {2016},
month = {7}
}