Unknown,Transcriptomics,Genomics,Proteomics

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Leukemia Cell Lines Induce Changes in Bone Marrow Stromal Cells

ABSTRACT: Bone marrow derived stromal cells (BMSCs) are a multipotent population that supports angiogenesis, wound healing, immunomodulation and plays an active role in the hematopoietic niche. On the other hand, they are also involved in the nurturing of bone marrow tumors and metastasis, showing a pro-tumorigenic behavior. BMSCs secrete a wide range of cytokines, growth factors and matrix proteins that are likely responsible for many of these effects. However, it is not clear whether this pro-tumorigenic behavior of BMSCs is induced by the tumor cells, neither in what extent the tumor cells affect the type and quantity of factors produced by BMSCs. To determine how tumor cells that arise from bone marrow affect the BMSCs, we selected three myeloid leukemia cell lines (TF-1, TF-1alpha and K562) and co-cultured them with BMSCs from healthy donors. We found that, under co-culture condition, the gene expression profiling of BMSCs revealed up-regulation of many pro-inflammatory signaling related genes, mainly IL-17 signaling-related genes. Moreover, IL-17 signaling-related cytokines CCL2 and IL8, were increased in co-culture supernatants. We conclude that BMSCs react to the presence of leukemia cells undergoing changes in the cytokine and chemokine secretion profile. Thus, BMSCs and leukemia cells both contribute to the creation of a competitive niche more favorable to leukemia stem cells. BMSCs from healthy donors were transwell co-cultured with three different myeloid leukemia cell lines: TF-1 (n=3), TF-1alpha (n=3) and K562 (n=3). A 1-um Transwell system (BDBiosciences, San Jose, CA USA) was used to maintain the cultured BMSC and leukemia cell populations separate from each other. As a control BMSCs were also transwell co-cultured under the same conditions with CD34+ cells (n=9) isolated from G-CSF-mobilized peripheral blood stem cells from healthy donors. An alternative co-culture method was used to analyze BMSCs and leukemia cells in direct contact: TF-1 (n=3), TF-alpha (n=3) and K562 (n=3). The two populations were cultured together in the same well without any membrane separation. BMSCs (n=18), TF-1 (n=3), TF-1alpha (n=3), K562 (n=3) and CD34+ (n=9) cells cultured alone (mono-cultures) were used as controls. Cells from both mono- and co-culture conditions were harvested at 4h, 10h, and 24h.

ORGANISM(S): Homo sapiens

SUBMITTER: PING JIN

PROVIDER: E-GEOD-45663 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Leukemia cells induce changes in human bone marrow stromal cells.

Civini Sara S Jin Ping P Ren Jiaqiang J Sabatino Marianna M Castiello Luciano L Jin Jianjian J Wang Huan H Zhao Yuanlong Y Marincola Francesco F Stroncek David D

Journal of translational medicine 20131204

<h4>Background</h4>Bone marrow stromal cells (BMSCs) are multipotent cells that support angiogenesis, wound healing, and immunomodulation. In the hematopoietic niche, they nurture hematopoietic cells, leukemia, tumors and metastasis. BMSCs secrete of a wide range of cytokines, growth factors and matrix proteins which contribute to the pro-tumorigenic marrow microenvironment. The inflammatory cytokines IFN-γ and TNF-α change the BMSC secretome and we hypothesized that factors produced by tumors o ...[more]

PMID: 24304929

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Dataset Information

Leukemia Cell Lines Induce Changes in Bone Marrow Stromal Cells

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Leukemia cells induce changes in human bone marrow stromal cells.

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