# Tungsten and Breast Cancer: Impact of the Tumor Microenvironment

> **NIH NIH P20** · UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR · 2020 · $265,125

## Abstract

Project Summary/Abstract
Tungsten is an emerging toxicant, due to increased human exposure, yet limited knowledge of the human
health risks. One large research gap is our lack of knowledge of the carcinogenic/tumorigenic risks of tungsten
exposure. Importantly, a few in vivo studies do suggest that tungsten can enhance tumor promotion. However,
more research is needed to determine which forms and routes of exposure of tungsten can drive tumorigenesis
and the underlying cellular/molecular mechanisms of action. An accidental exposure of breast cancer patients
to tungsten following experimental radiotherapy, prompted us to investigate the role of tungsten on breast
cancer progression and metastasis, by conducting an animal study using an aggressive orthotopic mammary
cancer mouse model. Oral tungstate exposure enhanced breast cancer metastasis to the lung and increased
growth at the metastatic site. Interestingly, tungsten-enhanced metastasis was associated with enhanced
stroma in the tumor microenvironment, importantly, cancer-associated fibroblasts (CAFs) that are known to
drive tumor progression. Our research identified, for the first time, a potential cellular mechanism of action for
tungsten-enhanced tumor promotion. However, what role the CAFs plays in this complex process remains to
be elucidated. This proposal will use a novel, integrative approach to investigate when and how tungsten
targets the tumor microenvironment to promote breast cancer. AIM 1 I will evaluate how different forms of
tungsten (oral tungstate, inhaled tungsten carbide and implantation tungsten metal fragments) target the tumor
microenvironment to affect breast cancer progression from initiation to metastasis. I will extend my initial
findings to determine how different forms of tungsten alter breast cancer development, growth and metastasis
to multiple sites including lung, liver, bone, and brain. AIM 2, I will measure CAF activation following tungsten
exposure in vitro. I will address the following questions. Can tungsten enhance CAF activation from stromal
precursors? Do tungsten-exposed CAFs enhance tumor cell invasion, growth, and immune cell recruitment?
And, does tungsten alter tumor cell cues to enhance CAF activation and/or recruitment? Finally, in AIM 3 I will
test the impact of tungsten-altered CAFs to enhance metastasis in an in vivo model. I will determine if
tungsten-altered CAFs promote metastasis and growth in the lung niche by answering the following questions.
What is the source of tungsten-enhanced CAFs in the lung niche? Do CAFs from the lung niche of tungsten-
exposed tumor-bearing mice have an altered cytokine/chemokine profile? And, are CAFs critical mediators of
tungsten-enhanced lung metastasis? Completion of this proposal will extend our toxicological knowledge of
tungsten to determine how different forms of tungsten impact breast cancer progression and define the role of
the tumor microenvironment, particularly CAFs in tungsten-enhanced breast t...

## Key facts

- **NIH application ID:** 9854030
- **Project number:** 1P20GM130422-01A1
- **Recipient organization:** UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR
- **Principal Investigator:** Alicia M. Bolt
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $265,125
- **Award type:** 1
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9854030

## Citation

> US National Institutes of Health, RePORTER application 9854030, Tungsten and Breast Cancer: Impact of the Tumor Microenvironment (1P20GM130422-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9854030. Licensed CC0.

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