Direct bone resorbing activity of murine myeloma cells

McDonald, D F; Schofield, Brian; Prezioso, Elena M.; Adams, Vicki L.; Frondoza, Carmelita G.; Trivedi, Sudhir M.; Craig, Caren; Humphrey, Richard L.

doi:10.1016/0304-3835(83)90145-3

Cited by 19 publications

(22 citation statements)

References 14 publications

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“…This most probably occurs through a coordinated interplay among various components within the myelomatous BM microenvironment that maintain conditions favoring tumor growth as well as bone destruction. Myeloma cells may be able to directly destroy bone, 30 and OCs can possess chromosomal abnormalities present in primary myeloma clones suggesting a fusion of these 2 cells. 31 Despite evidence of this direct tumor-bone interaction, we think that T cells play a critical role in this process as proposed in Figure 5.…”

Section: Discussionmentioning

confidence: 99%

A novel role of IL-17–producing lymphocytes in mediating lytic bone disease in multiple myeloma

Noonan

Marchionni

Anderson

et al. 2010

Blood

194

163

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IntroductionMultiple myeloma results from the clonal outgrowth of malignant plasma cells and is primarily confined to the bone marrow (BM). In addition to the direct effect of plasma cells on normal hematopoietic function, myeloma-induced lytic bone disease affects the majority of patients and represents a major comorbidity. [1][2][3] The interaction of malignant plasma cells with the surrounding stromal microenvironment mediated by increased receptor activator of nuclear factor-kappa B ligand (RANKL) production and reduced osteoprotegrin secretion plays a critical role in accelerating osteoclast (OC)-mediated bone resorption and destruction. 4,5 However, the putative role of additional factors of the bone destructive process is currently unknown.Immunologically, the BM possesses several unique properties. It is a reservoir of memory T cells with heightened antigen specificity 6,7 and is capable of effectively priming naive T-cell responses. 8 The non-tumor-bearing marrow also serves as a reservoir of regulatory T cells (Tregs). 9 In multiple myeloma, we have previously shown that marrow infiltrating lymphocytes (MILs) are more effectively activated and expanded, possess greater antitumor activity than peripheral blood lymphocytes (PBLs) from the same patients, and thus represent more suitable T cells for adoptive immunotherapy in this disease. 10,11 Considering these unique features of MILs, we hypothesized that factors must be present within the tumor microenvironment and absent in the non-tumor-bearing host that are critical in facilitating T-cell activation.Beyond the classic Th1 and Th2 subsets of helper T cells, Th17 T cells have recently been identified as important in the response to pulmonary and colonic bacterial infections as well as key mediators of pathology in numerous autoimmune conditions, including rheumatoid arthritis, systemic lupus erythematosis, and inflammatory bowel diseases. 12 These cells represent a newly defined lineage of T lymphocytes capable of producing interleukin-17 (IL-17) but not interferon-␥ (IFN-␥) or IL-4. As such, they are distinct from the canonical Th1 or Th2 lineages. 13 Th17 differentiation is mediated by transforming growth factor-␤ (TGF-␤) and IL-6. 14 In contrast, increased levels of IL-6 suppress Treg formation. 15 The critical role of IL-6 in the suppression of Treg differentiation and promotion of Th17 differentiation 15 raises the possibility that myeloma, known to produce significant amounts of IL-6, could alter the Th17/Treg balance. Considering the role of Th17 cells in autoimmune diseases and their recent implication in the bone destruction observed in rheumatoid arthritis, 16 we sought to determine whether MILs from myeloma patients produced IL-17 and whether this T-cell population contributed to the osteolytic bone disease in multiple myeloma. Methods SamplesBM and PBL samples were obtained from both myeloma patients (N ϭ 68) and normal donors (N ϭ 6) under informed consent in accordance with the Declaration of Helsinki with approval from the Institutional ...

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Section: Discussionmentioning

confidence: 99%

A novel role of IL-17–producing lymphocytes in mediating lytic bone disease in multiple myeloma

Noonan

Marchionni

Anderson

et al. 2010

Blood

194

163

View full text Add to dashboard Cite

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“…The results for the isografts rest on some assumptions. Retention or release of radioactive constituents has been widely applied for the purpose of studying bone formation and resorption both in uiuo and in uitro (Cohn & Gusmano 1967, Firschein & Alcock 1969, Klein et al 1983, McDonald et al 1983, Reeve et al 1976. In a pilot study we measured the radioactivity of transplants massively labelled with "Sr as compared to unlabelled transplants placed in rat musculature.…”

Section: Discussionmentioning

confidence: 99%

Bone formation enhanced by induction: Bone growth in titanium implants in rats

Rønningen

Solheim

Langeland

1985

Acta Orthopaedica Scandinavica

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“…An additional signal of increased RANKL production was generated by the treatment of myeloma cells with LPS, which can mimic bacterial infection in vivo. It seems likely that in the organisms of MM patients, myeloma cells may initiate bone resorption by acting as functional osteoclasts, as observed in mouse plasmacytoma (McDonald et al 1983).…”

Section: The Interaction Of Myeloma Cells With Bm Stroma Is Thought Tmentioning

confidence: 99%

Dysregulation of the Receptor Activator of NF-κB Ligand and Osteoprotegerin Production Influence the Apoptosis of Multiple Myeloma Patients’ Bone Marrow Stromal Cells Co-Cultured with Myeloma Cells

Zdzisińska

Bojarska‐Junak²,

Walter‐Croneck³

et al. 2010

Arch. Immunol. Ther. Exp.

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The interaction of multiple myeloma (MM) cells and bone marrow stromal cells (BMSCs) induces profound changes in the bone marrow environment, influencing osteoclastogenesis and MM cell survival. Differences in receptor activator of NF-kappaB ligand (RANKL) and osteoprotegerin (OPG) production in BMSCs derived from MM patients and control subjects and the apoptosis of BMSCs and MM cells in co-cultures of both cell types were examined. RANKL and OPG expressions were examined by ELISA and semiquantitative RT-PCR. Apoptosis of BMSCs after contact with RPMI8226 and U266 cells was measured by flow cytometry and the level of ALP activity by the spectrophotometric method. OPG production by BMSCs was significantly inhibited after direct contact with RPMI8226 cells. Production of soluble RANKL was enhanced and the increase was more significant in the BMSCs of the MM patients than in those of the controls. In co-cultures of BMSCs and MM cells, significant apoptosis was detected with a concomitant decrease in ALP activity. This apoptosis decreased significantly in the presence of RANK-Fc, an antagonist of RANKL. Disturbances in the RANKL/OPG system are more profound in the BMSCs of MM patients than in those of control subjects after direct contact with RPMI8226 cells. Moreover, direct contact with RPMI8226 and U266 cells induces apoptosis of BMSCs which is mediated by an overproduction of RANKL.

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Direct bone resorbing activity of murine myeloma cells

Cited by 19 publications

References 14 publications

A novel role of IL-17–producing lymphocytes in mediating lytic bone disease in multiple myeloma

A novel role of IL-17–producing lymphocytes in mediating lytic bone disease in multiple myeloma

Bone formation enhanced by induction: Bone growth in titanium implants in rats

Dysregulation of the Receptor Activator of NF-κB Ligand and Osteoprotegerin Production Influence the Apoptosis of Multiple Myeloma Patients’ Bone Marrow Stromal Cells Co-Cultured with Myeloma Cells

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