title: 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.
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.
authors.affiliation: Department of Clinical Medicine, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil; Hemotherapy Center of Ribeirão Preto, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil. Electronic address: lucasebsouza@usp.br.
authors.forename: Lucas E B
authors.initials: LE
authors.lastname: Souza
authors.affiliation: Department of Medicine - Nephrology, Laboratory of Clinical and Experimental Immunology, Federal University of São Paulo, São Paulo, SP, Brazil. Electronic address: gudaalmeida@gmail.com.
authors.forename: Danilo C
authors.initials: DC
authors.lastname: Almeida
authors.affiliation: Department of Biochemistry and Immunology, Basic and Applied Immunology Program, School of Medicine of Ribeirão Preto, University of São Paulo, Brazil. Electronic address: ueda.juliana@gmail.com.
authors.forename: Juliana N U
authors.initials: JN
authors.lastname: Yaochite
authors.affiliation: Department of Clinical Medicine, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil; Hemotherapy Center of Ribeirão Preto, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil. Electronic address: dimas@fmrp.usp.br.
authors.forename: Dimas T
authors.initials: DT
authors.lastname: Covas
authors.affiliation: Department of Genetics, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil. Electronic address: aparecidamfontes@usp.br.
authors.forename: Aparecida M
authors.initials: AM
authors.lastname: Fontes
mesh_terms: D061605:Administration, Intravenous; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D039481:CD11b Antigen / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000473:pathology; D002452:Cell Count; D049109:Cell Proliferation; D018920:Coculture Techniques; D042783:Endothelial Cells / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D008168:Lung / Q000473:pathology*; D008175:Lung Neoplasms / Q000556:secondary; D008546:Melanoma, Experimental / Q000473:pathology*; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D008810:Mice, Inbred C57BL; D039902:Multipotent Stem Cells / Q000166:cytology*; D022423:Myeloid Cells / Q000166:cytology*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D039481:CD11b Antigen; D019408:Platelet Endothelial Cell Adhesion Molecule-1