Pharmaceutical Sciences ETDs

Publication Date

Spring 5-10-2022

Abstract

The objective of this thesis project was to investigate the effects of tungsten on breast cancer metastasis to the bone niche, using the 4T1 orthotopic breast cancer model. Oral tungsten (15 ppm) exposure did not affect primary tumor growth. However, following tungsten exposure there were marked changes in the bone niche, including increased metastasis of 4T1 tumor cells and increased osteolysis. Further analysis of the bone niche indicates that enhanced metastasis is associated with a pro-tumorigenic immune suppressive environment, including increased number of granulocytic myeloid derived suppressor cells and increased gene expression of the pro-inflammatory cytokine IL-1β and the activated fibroblast marker α smooth muscle actin. These results suggest that tungsten accumulation in the bone is changing the bone niche to create a pro-tumor immune suppressive environment. The exact mechanisms behind this are multifactorial, but evidence suggests tungsten may be affecting breast cancer cells to enhance homing and colonization within the bone niche.

First Committee Member (Chair)

Alicia Bolt, PhD

Degree Name

Pharmaceutical Sciences

Second Committee Member

Helen Hathaway, PhD

Level of Degree

Masters

Third Committee Member

Matthew Campen, PhD

Department Name

College of Pharmacy

Language

English

Document Type

Thesis

Keywords

Tungsten, Breast Cancer, Metastasis, Bone, In vivo, mouse model

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