Evidence map›Paper›PMID 25324207›Full record

ArticleToxicological sciences : an official journal of the Society of Toxicology2015

Tungsten targets the tumor microenvironment to enhance breast cancer metastasis.

Alicia M Bolt, Valérie Sabourin, Manuel Flores Molina, Alice M Police, Luis Fernando Negro Silva, Dany Plourde, Maryse Lemaire, Josie Ursini-Siegel, Koren K Mann

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Toxicological sciences : an official journal of the Society of Toxicology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
1.3field-weighted citation impact, top 22% 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

17 citing papers in PubMed, 38 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Article
  6. Article
  7. Tungsten toxicity and carcinogenesis.Advances in pharmacology (San Diego, Calif.) · 2023
    Article
  8. Inhalation of Tungsten Metal Particulates Alters the Lung and Bone Microenvironments Following Acute Exposure.Toxicological sciences : an official journal of the Society of Toxicology · 2021
    Article
  9. Tungsten Increases Sex-Specific Osteoclast Differentiation in Murine Bone.Toxicological sciences : an official journal of the Society of Toxicology · 2021
    Article
  10. Environmental chemicals, breast cancer progression and drug resistance.Environmental health : a global access science source · 2020
    Review
  11. Article
  12. Review
  13. Article
  14. Tungsten: an Emerging Toxicant, Alone or in Combination.Current environmental health reports · 2016
    Review
  15. Article
  16. Article
  17. Article
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

9 authors at 2 institutions in 2 countries.

Alicia M Bolt*Lady Davis Institute for Medical Research, McGill University, Montréal, Québec, Canada, H3T 1E2, Department of Oncology, McGill University, Montréal, Québec, Canada, H2W 1S6, Pacific Breast Care Center, Costa Mesa, California, 92627, Division of Surgical Oncology, University of California, Irvine School of Medicine, Irvine, California, 92627; and Division of Experimental Medicine, McGill University, Montréal, Québec, Canada, H3A 1A3 *Lady Davis Institute for Medical Research, McGill University, Montréal, Québec, Canada, H3T 1E2, Department of Oncology, McGill University, Montréal, Québec, Canada, H2W 1S6, Pacific Breast Care Center, Costa Mesa, California, 92627, Division of Surgical Oncology, University of California, Irvine School of Medicine, Irvine, California, 92627; and Division of Experimental Medicine, McGill University, Montréal, Québec, Canada, H3A 1A3.
Valérie Sabourin*Lady Davis Institute for Medical Research, McGill University, Montréal, Québec, Canada, H3T 1E2, Department of Oncology, McGill University, Montréal, Québec, Canada, H2W 1S6, Pacific Breast Care Center, Costa Mesa, California, 92627, Division of Surgical Oncology, University of California, Irvine School of Medicine, Irvine, California, 92627; and Division of Experimental Medicine, McGill University, Montréal, Québec, Canada, H3A 1A3.
Manuel Flores Molina*Lady Davis Institute for Medical Research, McGill University, Montréal, Québec, Canada, H3T 1E2, Department of Oncology, McGill University, Montréal, Québec, Canada, H2W 1S6, Pacific Breast Care Center, Costa Mesa, California, 92627, Division of Surgical Oncology, University of California, Irvine School of Medicine, Irvine, California, 92627; and Division of Experimental Medicine, McGill University, Montréal, Québec, Canada, H3A 1A3.
Alice M Police*Lady Davis Institute for Medical Research, McGill University, Montréal, Québec, Canada, H3T 1E2, Department of Oncology, McGill University, Montréal, Québec, Canada, H2W 1S6, Pacific Breast Care Center, Costa Mesa, California, 92627, Division of Surgical Oncology, University of California, Irvine School of Medicine, Irvine, California, 92627; and Division of Experimental Medicine, McGill University, Montréal, Québec, Canada, H3A 1A3 *Lady Davis Institute for Medical Research, McGill University, Montréal, Québec, Canada, H3T 1E2, Department of Oncology, McGill University, Montréal, Québec, Canada, H2W 1S6, Pacific Breast Care Center, Costa Mesa, California, 92627, Division of Surgical Oncology, University of California, Irvine School of Medicine, Irvine, California, 92627; and Division of Experimental Medicine, McGill University, Montréal, Québec, Canada, H3A 1A3.
Luis Fernando Negro Silva*Lady Davis Institute for Medical Research, McGill University, Montréal, Québec, Canada, H3T 1E2, Department of Oncology, McGill University, Montréal, Québec, Canada, H2W 1S6, Pacific Breast Care Center, Costa Mesa, California, 92627, Division of Surgical Oncology, University of California, Irvine School of Medicine, Irvine, California, 92627; and Division of Experimental Medicine, McGill University, Montréal, Québec, Canada, H3A 1A3 *Lady Davis Institute for Medical Research, McGill University, Montréal, Québec, Canada, H3T 1E2, Department of Oncology, McGill University, Montréal, Québec, Canada, H2W 1S6, Pacific Breast Care Center, Costa Mesa, California, 92627, Division of Surgical Oncology, University of California, Irvine School of Medicine, Irvine, California, 92627; and Division of Experimental Medicine, McGill University, Montréal, Québec, Canada, H3A 1A3.
Dany Plourde*Lady Davis Institute for Medical Research, McGill University, Montréal, Québec, Canada, H3T 1E2, Department of Oncology, McGill University, Montréal, Québec, Canada, H2W 1S6, Pacific Breast Care Center, Costa Mesa, California, 92627, Division of Surgical Oncology, University of California, Irvine School of Medicine, Irvine, California, 92627; and Division of Experimental Medicine, McGill University, Montréal, Québec, Canada, H3A 1A3.
Maryse Lemaire*Lady Davis Institute for Medical Research, McGill University, Montréal, Québec, Canada, H3T 1E2, Department of Oncology, McGill University, Montréal, Québec, Canada, H2W 1S6, Pacific Breast Care Center, Costa Mesa, California, 92627, Division of Surgical Oncology, University of California, Irvine School of Medicine, Irvine, California, 92627; and Division of Experimental Medicine, McGill University, Montréal, Québec, Canada, H3A 1A3 *Lady Davis Institute for Medical Research, McGill University, Montréal, Québec, Canada, H3T 1E2, Department of Oncology, McGill University, Montréal, Québec, Canada, H2W 1S6, Pacific Breast Care Center, Costa Mesa, California, 92627, Division of Surgical Oncology, University of California, Irvine School of Medicine, Irvine, California, 92627; and Division of Experimental Medicine, McGill University, Montréal, Québec, Canada, H3A 1A3.
Josie Ursini-Siegel*Lady Davis Institute for Medical Research, McGill University, Montréal, Québec, Canada, H3T 1E2, Department of Oncology, McGill University, Montréal, Québec, Canada, H2W 1S6, Pacific Breast Care Center, Costa Mesa, California, 92627, Division of Surgical Oncology, University of California, Irvine School of Medicine, Irvine, California, 92627; and Division of Experimental Medicine, McGill University, Montréal, Québec, Canada, H3A 1A3 *Lady Davis Institute for Medical Research, McGill University, Montréal, Québec, Canada, H3T 1E2, Department of Oncology, McGill University, Montréal, Québec, Canada, H2W 1S6, Pacific Breast Care Center, Costa Mesa, California, 92627, Division of Surgical Oncology, University of California, Irvine School of Medicine, Irvine, California, 92627; and Division of Experimental Medicine, McGill University, Montréal, Québec, Canada, H3A 1A3 *Lady Davis Institute for Medical Research, McGill University, Montréal, Québec, Canada, H3T 1E2, Department of Oncology, McGill University, Montréal, Québec, Canada, H2W 1S6, Pacific Breast Care Center, Costa Mesa, California, 92627, Division of Surgical Oncology, University of California, Irvine School of Medicine, Irvine, California, 92627; and Division of Experimental Medicine, McGill University, Montréal, Québec, Canada, H3A 1A3.
Koren K Mann*Lady Davis Institute for Medical Research, McGill University, Montréal, Québec, Canada, H3T 1E2, Department of Oncology, McGill University, Montréal, Québec, Canada, H2W 1S6, Pacific Breast Care Center, Costa Mesa, California, 92627, Division of Surgical Oncology, University of California, Irvine School of Medicine, Irvine, California, 92627; and Division of Experimental Medicine, McGill University, Montréal, Québec, Canada, H3A 1A3 *Lady Davis Institute for Medical Research, McGill University, Montréal, Québec, Canada, H3T 1E2, Department of Oncology, McGill University, Montréal, Québec, Canada, H2W 1S6, Pacific Breast Care Center, Costa Mesa, California, 92627, Division of Surgical Oncology, University of California, Irvine School of Medicine, Irvine, California, 92627; and Division of Experimental Medicine, McGill University, Montréal, Québec, Canada, H3A 1A3 *Lady Davis Institute for Medical Research, McGill University, Montréal, Québec, Canada, H3T 1E2, Department of Oncology, McGill University, Montréal, Québec, Canada, H2W 1S6, Pacific Breast Care Center, Costa Mesa, California, 92627, Division of Surgical Oncology, University of California, Irvine School of Medicine, Irvine, California, 92627; and Division of Experimental Medicine, McGill University, Montréal, Québec, Canada, H3A 1A3 koren.mann@mcgill.ca.
University of California, Irvine · USMcGill University · CA

Funding

Canadian Institutes of Health Research MOP-111143Canadian Institutes of Health Research MOP-115000
6 · The paper itself

Abstract

The number of individuals exposed to high levels of tungsten is increasing, yet there is limited knowledge of the potential human health risks. Recently, a cohort of breast cancer patients was left with tungsten in their breasts following testing of a tungsten-based shield during intraoperative radiotherapy. While monitoring tungsten levels in the blood and urine of these patients, we utilized the 66Cl4 cell model, in vitro and in mice to study the effects of tungsten exposure on mammary tumor growth and metastasis. We still detect tungsten in the urine of patients' years after surgery (mean urinary tungsten concentration at least 20 months post-surgery = 1.76 ng/ml), even in those who have opted for mastectomy, indicating that tungsten does not remain in the breast. In addition, standard chelation therapy was ineffective at mobilizing tungsten. In the mouse model, tungsten slightly delayed primary tumor growth, but significantly enhanced lung metastasis. In vitro, tungsten did not enhance 66Cl4 proliferation or invasion, suggesting that tungsten was not directly acting on 66Cl4 primary tumor cells to enhance invasion. In contrast, tungsten changed the tumor microenvironment, enhancing parameters known to be important for cell invasion and metastasis including activated fibroblasts, matrix metalloproteinases, and myeloid-derived suppressor cells. We show, for the first time, that tungsten enhances metastasis in an animal model of breast cancer by targeting the microenvironment. Importantly, all these tumor microenvironmental changes are associated with a poor prognosis in humans.

Indexed as

Tumor MicroenvironmentAnimalsBiopsyBody BurdenBreast NeoplasmsCell Line, TumorCell MovementCell ProliferationChelating AgentsFemaleHumansInflammation MediatorsLung NeoplasmsMammographyMice, Inbred BALB CNeoplasm InvasivenessChelating AgentsInflammation Mediatorssodium tungstate(VI)Tungsten Compoundsbreast cancermetastasistumor microenvironmenttungsten

Identifiers

PMID25324207
PMCPMC4274385
OpenAlexW2119835079

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.