The cytokine-mediated crosstalk between primary human acute myeloid cells and mesenchymal stem cells alters the local cytokine network and the global gene expression profile of the mesenchymal cells
Interactions between acute myeloid leukemia (AML) blasts and neighboring stromal cells are important for disease development and chemosensitivity. However, the molecular mechanisms involved in the cytokine-mediated crosstalk between mesenchymal stem cells (MSCs) and AML cells are largely unknown. Le...
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| Format: | Article |
| Language: | English |
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Elsevier
2015-11-01
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| Series: | Stem Cell Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S187350611500121X |
| _version_ | 1818858354905186304 |
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| author | Håkon Reikvam Annette K. Brenner Karen Marie Hagen Knut Liseth Silje Skrede Kimberley Joanne Hatfield Øystein Bruserud |
| author_facet | Håkon Reikvam Annette K. Brenner Karen Marie Hagen Knut Liseth Silje Skrede Kimberley Joanne Hatfield Øystein Bruserud |
| author_sort | Håkon Reikvam |
| collection | DOAJ |
| description | Interactions between acute myeloid leukemia (AML) blasts and neighboring stromal cells are important for disease development and chemosensitivity. However, the molecular mechanisms involved in the cytokine-mediated crosstalk between mesenchymal stem cells (MSCs) and AML cells are largely unknown. Leukemic cells derived from 18 unselected AML patients were cultured with bone marrow MSCs derived from healthy donors; the populations then being separated by a semipermeable membrane. Coculture had only minor effects on MSC proliferation. The unique cytokine network in cocultures was determined by high constitutive MSC release of certain cytokines (especially IL-6 and vascular endothelial growth factor) and constitutive release of a wide range of soluble mediators by primary AML cells. However, the AML cell release varied considerably between patients, and these differences between patients were also reflected in the coculture levels even though supra-additive effects were seen for many mediators. These effects on the local cytokine network were dependent on a functional crosstalk between the two cell subsets. The crosstalk altered the global gene expression profile of the MSCs, especially expression of genes encoding proteins involved in downstream signaling from Toll like receptors, NFκB signaling and CCL/CXCL chemokine release. Thus, primary AML cells alter the functional phenotype of normal MSCs. |
| first_indexed | 2024-12-19T08:54:58Z |
| format | Article |
| id | doaj.art-c61cd7b682824ae29c989f9a8eba5eb0 |
| institution | Directory Open Access Journal |
| issn | 1873-5061 1876-7753 |
| language | English |
| last_indexed | 2024-12-19T08:54:58Z |
| publishDate | 2015-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Stem Cell Research |
| spelling | doaj.art-c61cd7b682824ae29c989f9a8eba5eb02022-12-21T20:28:38ZengElsevierStem Cell Research1873-50611876-77532015-11-0115353054110.1016/j.scr.2015.09.008The cytokine-mediated crosstalk between primary human acute myeloid cells and mesenchymal stem cells alters the local cytokine network and the global gene expression profile of the mesenchymal cellsHåkon Reikvam0Annette K. Brenner1Karen Marie Hagen2Knut Liseth3Silje Skrede4Kimberley Joanne Hatfield5Øystein Bruserud6Section for Hematology, Department of Clinical Science, University of Bergen, NorwaySection for Hematology, Department of Clinical Science, University of Bergen, NorwaySection for Hematology, Department of Clinical Science, University of Bergen, NorwayDepartment of Immunology and Transfusion Medicine, Haukeland University Hospital, Bergen, NorwayThe Norwegian Centre for Mental Disorders Research (NORMENT), K.G. Jebsen Centre for Psychosis Research, Department of Clinical Science, University of Bergen, NorwaySection for Hematology, Department of Clinical Science, University of Bergen, NorwaySection for Hematology, Department of Clinical Science, University of Bergen, NorwayInteractions between acute myeloid leukemia (AML) blasts and neighboring stromal cells are important for disease development and chemosensitivity. However, the molecular mechanisms involved in the cytokine-mediated crosstalk between mesenchymal stem cells (MSCs) and AML cells are largely unknown. Leukemic cells derived from 18 unselected AML patients were cultured with bone marrow MSCs derived from healthy donors; the populations then being separated by a semipermeable membrane. Coculture had only minor effects on MSC proliferation. The unique cytokine network in cocultures was determined by high constitutive MSC release of certain cytokines (especially IL-6 and vascular endothelial growth factor) and constitutive release of a wide range of soluble mediators by primary AML cells. However, the AML cell release varied considerably between patients, and these differences between patients were also reflected in the coculture levels even though supra-additive effects were seen for many mediators. These effects on the local cytokine network were dependent on a functional crosstalk between the two cell subsets. The crosstalk altered the global gene expression profile of the MSCs, especially expression of genes encoding proteins involved in downstream signaling from Toll like receptors, NFκB signaling and CCL/CXCL chemokine release. Thus, primary AML cells alter the functional phenotype of normal MSCs.http://www.sciencedirect.com/science/article/pii/S187350611500121XAcute myeloid leukemiaMesenchymal stem cellsCytokinesGene expressionChemokinesNFκBToll like receptors |
| spellingShingle | Håkon Reikvam Annette K. Brenner Karen Marie Hagen Knut Liseth Silje Skrede Kimberley Joanne Hatfield Øystein Bruserud The cytokine-mediated crosstalk between primary human acute myeloid cells and mesenchymal stem cells alters the local cytokine network and the global gene expression profile of the mesenchymal cells Stem Cell Research Acute myeloid leukemia Mesenchymal stem cells Cytokines Gene expression Chemokines NFκB Toll like receptors |
| title | The cytokine-mediated crosstalk between primary human acute myeloid cells and mesenchymal stem cells alters the local cytokine network and the global gene expression profile of the mesenchymal cells |
| title_full | The cytokine-mediated crosstalk between primary human acute myeloid cells and mesenchymal stem cells alters the local cytokine network and the global gene expression profile of the mesenchymal cells |
| title_fullStr | The cytokine-mediated crosstalk between primary human acute myeloid cells and mesenchymal stem cells alters the local cytokine network and the global gene expression profile of the mesenchymal cells |
| title_full_unstemmed | The cytokine-mediated crosstalk between primary human acute myeloid cells and mesenchymal stem cells alters the local cytokine network and the global gene expression profile of the mesenchymal cells |
| title_short | The cytokine-mediated crosstalk between primary human acute myeloid cells and mesenchymal stem cells alters the local cytokine network and the global gene expression profile of the mesenchymal cells |
| title_sort | cytokine mediated crosstalk between primary human acute myeloid cells and mesenchymal stem cells alters the local cytokine network and the global gene expression profile of the mesenchymal cells |
| topic | Acute myeloid leukemia Mesenchymal stem cells Cytokines Gene expression Chemokines NFκB Toll like receptors |
| url | http://www.sciencedirect.com/science/article/pii/S187350611500121X |
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