Pleitrophin Is Highly Expressed by Myeloma Cells, Elevated in the Serum of Myeloma Patients, and Is a New Autocrine Growth Factor for This B Cell Malignancy.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3349-3349
Author(s):  
Haiming Chen ◽  
Daocheng Zhu ◽  
Richard A. Campbell ◽  
Christine Pan James ◽  
Sonia Guangxu Li ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Expression Pattern ◽  
Cell Lines ◽  
Normal Control ◽  
Serum Levels ◽  
Myeloma Cell ◽  
Multiple Myeloma Cell ◽  
Restricted Expression Pattern ◽  
Control Bone

Abstract Pleitrophin (PTN) was originally described as a development regulatory cytokine. This protein regulates the growth of neuroectodermal and mesodermal cell lineages during early embryogenesis but becomes down-regulated during late phase of embryogenesis and shows a very restricted expression pattern in adult neural system. This protein has been recently shown to both induce angiogenesis and bind to syndecan. Thus, we determined whether this protein may be found in tumor cells from myeloma patients and its potential to influence their growth. First, we measured serum levels of PTN in myeloma (n=115) and age-matched controls (n=50) using an ELISA-based technique. PTN levels in the serum of myeloma patients were markedly elevated compared to the normal control group (P<0.02). The serum concentration of PTN in MM patients averaged 28 pg (range, 8 to 110 pg). In contrast, the control serum levels averaged only 12 pg (range, 0 to 20 pg. Interestingly, the PTN concentration in two patients with plasma leukemia was much higher than other multiple myeloma patients. Next, we analyzed the expression of PTN using RT-PCR on RNA from myeloma cell lines (RPMI8226, U266), and multiple myeloma patients’ and normal control bone marrow aspirates. Results showed that the PTN mRNA was strongly expressed in multiple myeloma cell lines, myeloma bone marrow samples but not in the normal control bone marrow specimens. In order to determine whether PTN stimulates multiple myeloma growth, we further cloned a whole PTN sense or anti-sense sequencing DNA into the multiple myeloma cell lines RPMI8226 and U266. Cells transduced with sense PTN showed markedly increased proliferation compared to cells transduced with antisense or vector alone. The role of PTN in hematological malignancies has not been previously defined. Due to the restricted expression pattern of PTN in adults, PTN is suggested as a potential new target for treatment of multiple myeloma. Further investigations are defining the prognostic value of PTN serum levels and the mechanism by which this cytokine drives myeloma growth.

scholarly journals Establishment of two interleukin 6 (B cell stimulatory factor 2/interferon beta 2)-dependent human bone marrow-derived myeloma cell lines.

1989 ◽  
Vol 169 (1) ◽  
pp. 339-344 ◽  
Author(s):  
S Shimizu ◽  
R Yoshioka ◽  
Y Hirose ◽  
S Sugai ◽  
J Tachibana ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Cell Lines ◽  
Myeloma Cell ◽  
Nuclear Antigen ◽  
Myeloma Cells ◽  
Multiple Myeloma Cell ◽  
Human Multiple Myeloma ◽  
Dependent Growth

Two IL-6-dependent human multiple myeloma cell lines, ILKM2 and ILKM3, were established from the bone marrow of patients with IgG-K multiple myeloma. Both cell lines had the typical morphology and immunocytochemical features of myeloma cells. The surface phenotype of both cell lines was PCA-1+, OKT10+, CD10(J-5)-, CD19(B4)-, CD20(B1)-, CD21(B2)-, and OKIa-1-. A monoclonal cytoplasmic Ig, IgG-K or K L chain, was positive in ILKM2 or ILKM3, respectively. EBV nuclear antigen was negative in both cell lines. They proliferated in the presence of macrophages or macrophage-derived factors (MDF). Among the recombinant cytokines examined, IL-6 most strongly augmented the growth of both cell lines. The anti-IL-6 antibody completely inhibited the IL-6-dependent growth and almost completely inhibited the MDF- or purified MDF-dependent growth of both cell lines, ILKM2 and ILKM3 are now being maintained in the culture medium containing 2 ng/ml rIL-6. These results suggest that IL-6 produced by macrophages may play an important role in the growth of myeloma cells in vivo and that macrophages or IL-6 can be used for establishing human myeloma cell lines.

Bak Binding to Bcl-xL and Not to Mcl-1 Is Associated with ABT-737 Sensitivity in Multiple Myeloma Cell Lines

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3675-3675
Author(s):  
Alejo A Morales ◽  
David Siefker ◽  
Shannon M Matulis ◽  
Delia M Gutman ◽  
Lawrence H Boise
Keyword(s):  
Multiple Myeloma ◽  
Expression Pattern ◽  
Cell Lines ◽  
Single Agent ◽  
Family Members ◽  
Myeloma Cell ◽  
Lower Sensitivity ◽  
Sensitive Cell ◽  
Multiple Myeloma Cell ◽  
Induced Apoptosis

Abstract ABT-737 is a Bad-like BH3 mimetic and an effective inhibitor of the anti-apoptotic Bcl-2 family members Bcl-2, Bcl-xL and Bcl-w, but not Mcl-1. Recent studies have shown this new drug as a promising anti-cancer agent with activity in multiple myeloma cells. The purpose of this study was to evaluate the role of Bcl-2 family members in both determining the sensitivity and the mechanism of action of ABT-737 in multiple myeloma cell lines. ABT-737, as a single agent, induced apoptosis in six myeloma cell lines, although the sensitivity was quite different among cell lines. Three cell lines 8226/S, MM.1s and KMS18, were highly sensitive to ABT-737 with EC50 values of 0.30, 0.39 and 0.58 μM, respectively. In contrast, three cell lines, KMS11, U266 and OPM2 displayed lower sensitivity to the drug with EC50 values of 1.60, 2.58 and 2.57 μM ABT-737. No correlation between the sensitivity to ABT-737 and the expression pattern of the Bcl-2 family members was found. Interestingly, Mcl-1, a critical anti-apoptotic protein involved in myeloma cell survival that has also been shown to confer resistance to ABT-737, did not correlate with sensitivity to the drug. Bfl-1, an anti-apoptotic Bcl-2 family member with similar functions to Mcl-1, was only expressed in two sensitive cell lines, MM.1s and KMS18. Since the expression pattern did not reveal any strong correlation, we determined the effects of ABT-737 on association of Bcl-2 proteins. Co-immunoprecipitation experiments in MM.1s and KMS11, demonstrated that ABT-737 released Bak and Bim from Bcl-xL and Bim from Bcl-2 while no change was observed for Bak and Bim bound to Mcl-1. A closer look at the interaction of Bcl-2 family members revealed that Bak is equally bound to Mcl-1 and Bcl-xL in the less sensitive cell lines while it is primarily bound to Bcl-xL in the more sensitive cell lines 8226/S and KMS18. Interestingly, Bak in equally bound to Mcl-1 and Bcl-xL in MM.1s, the third sensitive cell line; however, Bim is also highly bound to Bcl-xL, suggesting an easier release of Bak and Bim by ABT-737 from a Bim-primed-Bcl-xL. Consistent with this idea, Bcl-xL overexpression significantly protected 8226/S but not KMS11 from ABT-737-induced death. Additionally, while silencing of Bim significantly protected MM.1s and KMS11 from ABT-737-induced apoptosis, release of Bak from Bcl-xL was not observed after Bim silencing in the MM.1s cells. Together these data suggest that the interaction pattern not the expression pattern of Bcl-2 proteins is a more accurate measure of ABT-737 function in cells. This is important in diseases like multiple myeloma where Mcl-1 in addition to other anti-apoptotic Bcl-2 proteins are typically expressed.

Bone marrow mesenchymal stem cells regulate stemness of multiple myeloma cell lines via BTK signaling pathway

2017 ◽  
Vol 57 ◽  
pp. 20-26 ◽  
Author(s):  
Pan Zhao ◽  
Yafang Chen ◽  
Zhijie Yue ◽  
Ying Yuan ◽  
Xiaofang Wang
Keyword(s):  
Stem Cells ◽  
Multiple Myeloma ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Signaling Pathway ◽  
Cell Lines ◽  
Myeloma Cell ◽  
Multiple Myeloma Cell ◽  
Marrow Mesenchymal Stem Cells

Bone sialoprotein mRNA and protein expression in human multiple myeloma cell lines and patients

2000 ◽  
Vol 111 (4) ◽  
pp. 1118-1121 ◽  
Author(s):  
A. Bellahcene ◽  
I. Van Riet ◽  
C. de Greef ◽  
N. Antoine ◽  
M. F. Young ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Protein Expression ◽  
Cell Lines ◽  
Myeloma Cell ◽  
Bone Sialoprotein ◽  
Multiple Myeloma Cell ◽  
Human Multiple Myeloma ◽  
Mrna And Protein Expression

The oral protein-kinase Cβinhibitor enzastaurin (LY317615) suppresses signalling through the AKT pathway, inhibits proliferation and induces apoptosis in multiple myeloma cell lines

2008 ◽  
Vol 49 (7) ◽  
pp. 1374-1383 ◽  
Author(s):  
Antonino Neri ◽  
Sandra Marmiroli ◽  
Pierfrancesco Tassone ◽  
Luigia Lombardi ◽  
Lucia Nobili ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Protein Kinase ◽  
Cell Lines ◽  
Myeloma Cell ◽  
Akt Pathway ◽  
Multiple Myeloma Cell

scholarly journals Establishment of Cell Lines from Both Myeloma Bone Marrow and Plasmacytoma: SNU_MM1393_BM and SNU_MM1393_SC from a Single Patient

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Youngil Koh ◽  
Woo-June Jung ◽  
Kwang-Sung Ahn ◽  
Sung-Soo Yoon
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Cell Lines ◽  
Mononuclear Cells ◽  
Cultured Cells ◽  
Clonal Evolution ◽  
Myeloma Cell ◽  
Mouse Bone Marrow ◽  
Single Patient ◽  
U266 Cell

Purpose.We tried to establish clinically relevant human myeloma cell lines that can contribute to the understanding of multiple myeloma (MM).Materials and Methods.Mononuclear cells obtained from MM patient’s bone marrow were injected via tail vein in an NRG/SCID mouse. Fourteen weeks after the injection, tumor developed at subcutis of the mouse. The engraftment of MM cells into mouse bone marrow (BM) was also observed. We separated and cultured cells from subcutis and BM.Results.After the separation and culture of cells from subcutis and BM, we established two cell lines originating from a single patient (SNU_MM1393_BM and SNU_MM1393_SC). Karyotype of the two newly established MM cell lines showed tetraploidy which is different from the karyotype of the patient (diploidy) indicating clonal evolution. In contrast to SNU_MM1393_BM, cell proliferation of SNU_MM1393_SC was IL-6 independent. SNU_MM1393_BM and SNU_MM1393_SC showed high degree of resistance against bortezomib compared to U266 cell line. SNU_MM1393_BM had the greater lethality compared to SNU_MM1393_SC.Conclusion.Two cell lines harboring different site tropisms established from a single patient showed differences in cytokine response and lethality. Our newly established cell lines could be used as a tool to understand the biology of multiple myeloma.

Simvastatin Induces Death of Multiple Myeloma Cell Lines

2004 ◽  
Vol 52 (5) ◽  
pp. 335-344 ◽  
Author(s):  
Naomi Gronich ◽  
Liat Drucker ◽  
Hava Shapiro ◽  
Judith Radnay ◽  
Shai Yarkoni ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Multiple Myeloma ◽  
Cell Death ◽  
Cell Lines ◽  
Myeloma Cell ◽  
Cytoplasmic Calcium ◽  
Multiple Myeloma Cell ◽  
Cycle Arrest ◽  
Rpmi 8226

BackgroundAccumulating reports indicate that statins widely prescribed for hypercholesteromia have antineoplastic activity. We hypothesized that because statins inhibit farnesylation of Ras that is often mutated in multiple myeloma (MM), as well as the production of interleukin (IL)-6, a key cytokine in MM, they may have antiproliferative and/or proapoptotic effects in this malignancy.MethodsU266, RPMI 8226, and ARH77 were treated with simvastatin (0-30 μM) for 5 days. The following aspects were evaluated: viability (IC50), cell cycle, cell death, cytoplasmic calcium ion levels, supernatant IL-6 levels, and tyrosine kinase activity.ResultsExposure of all cell lines to simvastatin resulted in reduced viability with IC50s of 4.5 μM for ARH77, 8 μM for RPMI 8226, and 13 μM for U266. The decreased viability is attributed to cell-cycle arrest (U266, G1; RPMI 8226, G2M) and cell death. ARH77 underwent apoptosis, whereas U266 and RPMI 8226 displayed a more necrotic form of death. Cytoplasmic calcium levels decreased significantly in all treated cell lines. IL-6 secretion from U266 cells was abrogated on treatment with simvastatin, whereas total tyrosine phosphorylation was unaffected.ConclusionsSimvastatin displays significant antimyeloma activity in vitro. Further research is warranted for elucidation of the modulated molecular pathways and clinical relevance.

scholarly journals The effects on growth and survival of IL‐6 can be dissociated in the U‐266‐1970/U‐266‐1984 and HL407E/HL407L human multiple myeloma cell lines

1997 ◽  
Vol 98 (1) ◽  
pp. 126-133 ◽  
Author(s):  
Helena Spets ◽  
Helena Jernberg‐Wiklund ◽  
Clara Sambade ◽  
Ola Söderberg ◽  
Kenneth Nilsson
Keyword(s):  
Multiple Myeloma ◽  
Cell Lines ◽  
Myeloma Cell ◽  
Growth And Survival ◽  
Multiple Myeloma Cell ◽  
Human Multiple Myeloma

Synergism between gemcitabine and low LET (gamma-rays), but not high-let alpha-particles on multiple myeloma cell lines

2004 ◽  
Vol 60 ◽  
pp. S373-S373
Author(s):  
S SUPIOT ◽  
F THILLAYS ◽  
E RIO ◽  
S GOUARD ◽  
M MAHE ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Cell Lines ◽  
Gamma Rays ◽  
Myeloma Cell ◽  
Alpha Particles ◽  
Multiple Myeloma Cell ◽  
High Let
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