Bone marrow stromal cells and interleukin-7 induce coordinate expression of the BP-1/6C3 antigen and pre-B cell growth

1990 ◽  
Vol 2 (8) ◽  
pp. 697-705 ◽  
Author(s):  
Pamela A. Welch ◽  
Peter D. Burrows ◽  
Anthony Namen ◽  
Steven Gillis ◽  
Max D. Cooper
Keyword(s):  
Bone Marrow ◽  
Cell Growth ◽  
B Cell ◽  
Stromal Cells ◽  
Bone Marrow Stromal Cells ◽  
Marrow Stromal Cells ◽  
Coordinate Expression ◽  
Interleukin 7

Crosstalk between Chronic Lymphocytic Leukemia (CLL) B-Cells and Marrow Stromal Cells: Implication for CLL B-Cell Activation and Survival.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 337-337
Author(s):  
Wei Ding ◽  
Grzegorz S. Nowakowski ◽  
Jennifer L. Abrahamzon ◽  
Linda E. Wellik ◽  
Asish K. Ghosh ◽  
...  
Keyword(s):  
Bone Marrow ◽  
B Cells ◽  
Growth Factor ◽  
B Cell ◽  
Stromal Cells ◽  
Bone Marrow Stromal Cells ◽  
Marrow Stromal Cells ◽  
Drug Induced ◽  
Cd38 Expression ◽  
The Mean

Abstract It is believed that malignant cells “condition” the microenvironment to facilitate tumor cell survival. We hypothesized that crosstalk between CLL B-cells and marrow stromal cells impacts both cell types bi-directionally and ultimately contributes to leukemic cell apoptotic resistance. To test this hypotheses, bone marrow stromal cells from core bone biopsies from CLL patients were isolated and cultured using methods we have previously described (Leuk Res 2007 31(7):899). Subsequently, we determined the impact of co-culture on CLL B-cell features including apoptosis and CD38 expression. In addition, we evaluated the release of angiogenic cytokines on co-culture and signal events in the stromal cells. Immunophenotyping demonstrated that cultured bone biopsy derived stromal cells were CD73+, CD105+, CD146+, CD14−, CD45−, CD34−, HLA-DR-, suggesting they were mesenchymal stem cells (MSC). Co-culture of these MSC with CLL B-cells protected CLL B-cells from both spontaneous apoptosis (SA) and drug-induced (fludarabine and chlorambucil) apoptosis (DA). For SA, the mean survival of CLL B-cells with or without co-culture of MSC for 5 days were 56.9 ± 10.0 and 7.7 ±3.7 (p<0.05), respectively. When CLL B cells were treated with fludarabine or chlorambucil, the fraction of CLL cells tightly adherent to MSC (TA-CLL) showed higher survival than a less adherent but viable fraction of CLL B-cells. The mean survival of TA-CLL cells treated with 10 μM of fludarabine for 48 hours in the presence of MSC were 67.5 ± 3.6 vs 29.8 ± 11.1 without MSC (P<0.05), respectively. When CLL cells with evidence for CD38 expression were co-cultured with MSC, both the percentage of CD38 positive cells and level of expression of CD38 per cell were up-regulated (mean fold change: CD38 percentage, 2.7, p<0.05; CD38 MFI, 1.9, p<0.05) after 2 weeks. In contrast, the CD38 percentage and expression were not changed in cells with minimal CD38 expression when these CLL B-cells were co-cultured with MSC. In addition, co-culture of MSC with CLL cells induced rapid ERK and AKT phosphorylation (within 30 min) in the MSC on immunoblot analysis. When CLL B cells and MSCs were cultured in transwells, the activation of ERK and AKT in MSC occurred at similar levels, indicating that activation of MSC was mediated by soluble factors. In addition, co-culture led to increased secretion of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) as well as a decrease of thrombospondin-1 (TSP-1) in the culture medium. These findings confirm that co-culture of CLL B-cells and MSC culminates in “angiogenic switch.” Taken together, these results strongly suggest interactions between MSC and CLL B cells are a bi-directional process. In leukemic cells, the interaction not only protects against spontaneous and drug induced apoptosis but also leads to an increase in CD38 expression consistent with an activated status. In MSC, the interaction leads to activation of ERK and AKT. Co-culture also facilitates angiogenic switching. These results underscore the dynamic and complex nature of the interactions between bone marrow stromal cells and CLL B-cells. Further studies are needed to dissect how crosstalk between CLL B-cells and MSC relates to disease progression, and determines whether these interactions can be targeted with therapeutic intent.

Human bone marrow stromal cells enhance breast cancer cell growth rates in a cell line-dependent manner when evaluated in 3D tumor environments

2007 ◽  
Vol 254 (2) ◽  
pp. 255-264 ◽  
Author(s):  
A. Kate Sasser ◽  
Bethany L. Mundy ◽  
Kristen M. Smith ◽  
Adam W. Studebaker ◽  
Amy E. Axel ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bone Marrow ◽  
Cell Growth ◽  
Stromal Cells ◽  
Bone Marrow Stromal Cells ◽  
Marrow Stromal Cells ◽  
Dependent Manner ◽  
Cancer Cell Growth ◽  
Breast Cancer Cell Growth ◽  
A Cell

scholarly journals Bone marrow stromal cells modulate both kappa light chain and Ly1 antigen expression on Ly1+ pre-B cell lines in vitro

Blood ◽  
1990 ◽  
Vol 76 (2) ◽  
pp. 383-392 ◽  
Author(s):  
MG Kruger ◽  
RL Riley ◽  
EA Riley ◽  
JM Elia
Keyword(s):  
Bone Marrow ◽  
B Cells ◽  
B Cell ◽  
Cell Lines ◽  
Stromal Cells ◽  
Bone Marrow Stromal Cells ◽  
Marrow Stromal Cells ◽  
Light Chains ◽  
Bone Marrow Cultures ◽  
Marrow Cultures

Abstract Murine Ly1+ pre-B cell lines, including 70Z/3 and three pre-B cell lines derived from long-term bone marrow cultures, exhibited selective adherence to bone marrow stromal cells. In contrast, splenic B cells, the A20 B-cell lymphoma, and four Ly1- B cell lines derived from long- term bone marrow cultures failed to adhere substiantially to bone marrow cultures failed to adhere substiantially to bone marrow stroma. Ly1+ pre-B cell lines were induced to express kappa light chains by exposure to either lipopolysaccharide (LPS), recombinant interleukin-1 (IL-1), or stromal cells. However, induction of kappa light chains failed to prevent pre-B cell adherence to stromal cells. Supernatants derived from primary bone marrow stromal cells decreased Ly1 expression on the Ly1+ pre-B cell lines. These experiments suggest that (1) expression of immunoglobulin light chains by developing Ly1+ pre-B cells is mediated by bone marrow stromal cells; (2) loss of specific adherence to stroma is progressive and occurs post-light chain induction; and (3) soluble products of stromal cells may downregulate expression of surface Ly1 on otherwise Ly1+ pre-B cells. The importance of these observations to the development of both the Ly1- and Ly1+ B cell lineages in the mouse is discussed.

Induction of indoleamine-2,3 dioxygenase in bone marrow stromal cells inhibits myeloma cell growth

2012 ◽  
Vol 138 (11) ◽  
pp. 1821-1830 ◽  
Author(s):  
Sabine Pfeifer ◽  
Martin Schreder ◽  
Arnold Bolomsky ◽  
Sebastian Graffi ◽  
Dietmar Fuchs ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cell Growth ◽  
Stromal Cells ◽  
Bone Marrow Stromal Cells ◽  
Myeloma Cell ◽  
Marrow Stromal Cells ◽  
Indoleamine 2,3 Dioxygenase

scholarly journals Impaired Ability of Bone Marrow Stromal Cells to Support B-Lymphopoiesis With Age

Blood ◽  
1998 ◽  
Vol 91 (1) ◽  
pp. 75-88 ◽  
Author(s):  
Robert P. Stephan ◽  
Colette R. Reilly ◽  
Pamela L. Witte
Keyword(s):  
Bone Marrow ◽  
Stromal Cells ◽  
Bone Marrow Stromal Cells ◽  
Lymphoid Cells ◽  
Marrow Stromal Cells ◽  
Cell Contact ◽  
B Lymphopoiesis ◽  
Interleukin 7 ◽  
Age Related ◽  
B Lymphoid

B-lymphopoiesis decreases with age. We studied how aging affects bone marrow stromal cells, because they provide the growth factors and cell contacts required for B-lymphopoiesis. No differences were noted in the cell-surface phenotype of young and old primary-cultured stromal cells. Fluorescence-activated cell sorter-purified stromal cells from old mice were deficient in the ability to support the proliferation of interleukin-7 (IL-7)–specific B-lymphoid cell lines. The kinetics of this response indicated that IL-7 was not immediately available from stromal cells of either age and was further delayed on aged stromal cells. The levels of IL-7 protein within stromal cells were equivalent between young and old animals, suggesting that the production of IL-7 was not altered by aging. Negligible amounts of IL-7 were found either freely secreted or in the extracellular matrix of cultures of young and old marrow. Contact between the lymphoid cells and the primary stromal cells was required for detectable proliferation, suggesting that cell contact was required for the release of IL-7. We propose that stromal cells regulate B-lymphopoiesis by limiting the amount of IL-7 available to the developing precursors. Therefore, we conclude that the age-related decrease in the function of bone marrow stromal cells is related to the impaired release of IL-7.

Rooting into the Soil, a Model for the Role of Sox4 in Leukemia

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3794-3794
Author(s):  
Saradhi Mallampati ◽  
Baohua Sun ◽  
Yun Gong ◽  
Enze Wang ◽  
M. James You ◽  
...  
Keyword(s):  
Bone Marrow ◽  
B Cells ◽  
B Cell ◽  
Stromal Cells ◽  
Bone Marrow Stromal Cells ◽  
Leukemic Cell ◽  
Marrow Stromal Cells ◽  
Leukemic Cells ◽  
Cell Stage

Abstract Development and progression of leukemia requires interaction of leukemia-initiating cells with their bone marrow niches. The niches serve as the nursery and shelter for the leukemic cells, which can result in drug resistance, disease recurrence, and minimal residual disease, the most important causes for the death of patients with leukemia. Therefore, obliteration of the interaction between the leukemic cells and their niches is of utmost importance in eradicating leukemic cells during therapy to cure the disease. However, little is currently known of the molecular mechanisms underlying the interaction of the two types of cells. Sox4, a SRY-related HMG-box containing transcription factor that is vital during development, plays an important role in leukemia. Published mouse studies demonstrated that increased expression of Sox4 was associated with leukemogenesis. We determined the expression levels of Sox4 by real-time RT-PCR in 100 human leukemic samples and found high levels of expression in B- and T-ALL, but not in AML, CML, CLL, Sezary syndrome, or T cell prolymphocytic leukemia. In accordance, 7 of the 8 ALL cell lines (the exception was 697) we tested showed high expression levels of Sox4, but AML cell lines, normal mature B cells, T cells, and bone marrow CD34+ cells had low levels of expression. Since the majority of clinical B-ALL cases correspond to the pre-B cell stage, we investigated the role of Sox4 in a pre-B cell line (Nalm6) by lentivirus-mediated RNAi. Remarkably, knockdown of Sox4 in Nalm6 cells caused 70% reduction in the formation of leukemic cell clusters under the monolayer of co-cultured M2-10B4 bone marrow stromal cells, a phenomenon known as pseudo-emperipolesis. Similar results were obtained with ex vivo cultured bone marrow cells from conditional Sox4 knockout mice that displayed B cell developmental arrest at the transition from pro-B to pre-B cell stage and an absence of pre-B cells. These findings suggested that Sox4 is required for the interaction of the developing B cells or leukemic cells with bone marrow stromal cells, a component of the bone marrow niche. Since CXCR4/SDF1-mediated “homing” is known to be required for pseudo-emperipolesis, we tested the effect of Sox4 on Nalm6 cell migration toward SDF1 gradient and found that Sox4 did not affect the migration, suggesting that Sox4 is not acting through “homing”. Instead, our data indicated that the role of Sox4 in the interaction of leukemic cells with stromal cells is most likely mediated by its ability in enhancing the adhesion of the leukemic cells because we found that lentivirus-medicated overexpression of Sox4 in the 697 B cell line caused the suspension cells to display a spindle and adhesive morphology. In addition, 21% of the putative Sox4 downstream genes that we identified by multiple sets of gene expression microarray experiments are known to be involved in cell adhesion. Moreover, we found that the changes in gene expression profile of leukemic cells upon Sox4 knockdown or overexpression significantly overlap with the changes in response to the presence of bone marrow stromal cells in co-culture, indicating that Sox4 pathways are involved in leukemic cell response to stromal cell signaling. Based on these findings we hypothesize that deletion of Sox4 abolishes the interaction between the developing lymphocytes and their niches during lymphopoiesis. Conversely, overexpression of Sox4 may enforce these cells to over-interact with the niches so that they are overexposed to local growth factor stimuli. If superimposed with other genetic and/or epigenetic changes in the developing lymphocytes, such over-interaction may result in the development of leukemia. In case of established leukemia, such over-interaction may lead to the enhanced protection of leukemic cells by their niches. Therefore, the role of Sox4 in the interaction of developing lymphocytes or leukemic cells with their niches is like “rooting into the soil” of a growing tree, abbreviated as “rooting”.

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