Intravenous administration of bone marrow-derived multipotent mesenchymal stromal cells enhances the recruitment of CD11b(+) myeloid cells to the lungs and facilitates B16-F10 melanoma colonization

Intravenous administration of bone marrow-derived multipotent mesenchymal stromal cells enhances the recruitment of CD11b(+) myeloid cells to the lungs and facilitates B16-F10 melanoma colonization

Author Souza, Lucas E. B. Google Scholar
Almeida, Danilo C. Autor UNIFESP Google Scholar
Yaochite, Juliana N. U. Google Scholar
Covas, Dimas T. Google Scholar
Fontes, Aparecida M. Google Scholar
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(+) 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(+) myeloid cells and tumor cells. (C) 2015 Elsevier Inc. All rights reserved.
xmlui.dri2xhtml.METS-1.0.item-coverage San Diego
Language English
Sponsor Sao Paulo Research Foundation (FAPESP)
Coordination for Improvement of Higher Education Personnel (CAPES)
National Counsel of Technological and Scientific Development (CNPq)
Grant number FAPESP: 2008/08944-0
CNPq: 310619/2012-2
Date 2016
Published in Experimental Cell Research. San Diego, v. 345, n. 2, p. 141-149, 2016.
ISSN 0014-4827 (Sherpa/Romeo, impact factor)
Publisher Elsevier Inc
Extent 141-149
Origin http://dx.doi.org/10.1016/j.yexcr.2015.05.021
Access rights Closed access
Type Article
Web of Science ID WOS:000380179600004
URI https://repositorio.unifesp.br/handle/11600/57538

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