Evidence map›Paper›PMID 19779066›Full record

ArticleDisease models & mechanisms

A murine model of myeloma that allows genetic manipulation of the host microenvironment.

Jessica A Fowler, Gregory R Mundy, Seint T Lwin, Conor C Lynch, Claire M Edwards

Open access · bronzeAbstract read
In one paragraph

Article in Disease models & mechanisms. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
1.5field-weighted citation impact, top 17% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

33 citing papers in PubMed, 51 citations in OpenAlex.

  1. Article
  2. Article
  3. LILRB4 on multiple myeloma cells promotes bone lesion by p-SHP2/NF-κB/RELT signal pathway.Journal of experimental & clinical cancer research : CR · 2024
    Article
  4. Endogenous CD28 drives CAR T cell responses in multiple myeloma.bioRxiv : the preprint server for biology · 2024
    Article
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  12. Sprague DawleyMolecular cancer therapeutics · 2018
    Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 1 institution in 1 country.

Jessica A FowlerVanderbilt Center for Bone Biology, Department of Cancer Biology, Vanderbilt University, Nashville, TN 37232, USA.
Gregory R Mundy
Seint T Lwin
Conor C Lynch
Claire M Edwards
Vanderbilt University · US

Funding

Tumor Immunology and Microenvironment Research ProgramP30CA068485 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI MATTHEW J TYSKA · 1995 to 2026
$172.8M
Translational Analysis CoreP30DK058404 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI RICHARD M. PEEK · 2002 to 2026
$29.9M
TUMORS EFFECTS ON THE SKELETONP01CA040035 · NCI · VANDERBILT UNIVERSITY · PI SUN, LUZHE · 1985 to 2010
$11.0M
NCI NIH HHS P01 CA040035NCI NIH HHS P01 CA-40035NCI NIH HHS P30 CA068485NCI NIH HHS P30 CA68485NIDDK NIH HHS DK058404NIDDK NIH HHS P30 DK058404
6 · The paper itself

Abstract

Multiple myeloma, and the associated osteolytic bone disease, is highly dependent upon cellular interactions within the bone marrow microenvironment. A major limitation of existing myeloma models is the requirement for a specific host strain of mouse, preventing molecular examination of the bone marrow microenvironment. The aim of the current study was to develop a model of myeloma in which the host microenvironment could be modified genetically. The Radl 5T murine model of myeloma is well characterized and closely mimics human myeloma. In the current study, we demonstrate 5T myeloma establishment in recombination activating gene 2 (RAG-2)-deficient mice, which have improper B- and T-cell development. Importantly, these mice can be easily bred with genetically modified mice to generate double knockout mice, allowing manipulation of the host microenvironment at a molecular level. Inoculation of 5TGM1 myeloma cells into RAG-2(-/-) mice resulted in myeloma development, which was associated with tumor growth within bone and an osteolytic bone disease, as assessed by microcomputed tomography (microCT), histology and histomorphometry. Myeloma-bearing RAG-2(-/-) mice displayed many features that were similar to both human myeloma and the original Radl 5T model. To demonstrate the use of this model, we have examined the effect of host-derived matrix metalloproteinase 9 (MMP-9) in the development of myeloma in vivo. Inoculation of 5TGM1 myeloma cells into mice that are deficient in RAG-2 and MMP-9 resulted in a reduction in both tumor burden and osteolytic bone disease when compared with RAG-2-deficient wild-type myeloma-bearing mice. The establishment of myeloma in RAG-2(-/-) mice permits molecular examination of the host contribution to myeloma pathogenesis in vivo.

Indexed as

Disease Models, AnimalAnimalsBone DiseasesDNA-Binding ProteinsFemaleFemurGenetic TechniquesImmunohistochemistryMatrix Metalloproteinase 9MiceMice, Inbred C57BLMice, TransgenicMultiple MyelomaTibiaTomography, X-Ray ComputedDNA-Binding ProteinsMatrix Metalloproteinase 9Rag2 protein, mouse

Identifiers

PMID19779066
PMCPMC2776114
OpenAlexW2151469370

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.