Investigating cancer cell dormancy and recurrence in the bone marrow niche

Casson, Jake (2020) Investigating cancer cell dormancy and recurrence in the bone marrow niche. PhD thesis, University of Glasgow.

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Abstract

Breast cancer is the most commonly diagnosed form of cancer in women. The spread of metastatic cancer cells to secondary sites, such as the bone marrow, is the leading cause of mortality. Upon entering the bone marrow, disseminated breast cancer cells enter a period of cycling quiescence, termed dormancy. Here, cells are able to reside in the new environment for years before re-entering a growth phase, known as recurrence.
The relationship between these breast cancer cells and resident mesenchymal stem cells (MSCs) is of clinical importance. MSCs have been implicated in the initiation of breast cancer dormancy. The precise mechanism of recurrence is not known, but there is evidence to suggest the relationship between breast cancer and MSCs is of importance. Research has traditionally used two-dimensional culture techniques, however these models lack the complexity and three-dimensional nature of the bone marrow environment.
The project aimed to develop a novel, bio-responsive in vitro three-dimensional bone marrow model. Magnetic nanoparticle-loaded breast cancer and mesenchymal stem cells were levitated using an external magnetic field to form multicellular spheroids. These spheroids were subsequently located within a Type I collagen gel. The breast cancer cells within the spheroid exhibited quiescent behaviour when cultured in the three-dimensional environment when exposed to MSC-derived extracellular vesicles. This quiescent behaviour was reversed when the breast cancer spheroids were exposed to cytokines IL-6 and TGFβ, associated with cellular repair.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Additional Information: TAD requested 30 March 20 MC
Keywords: 3D, breast cancer, stem cells, in vitro, model.
Subjects: Q Science > QH Natural history > QH301 Biology
Colleges/Schools: College of Medical Veterinary and Life Sciences > School of Life Sciences > Life Sciences Biomolecular Science
Supervisor's Name: Berry, Dr. Catherine and Dalby, Professor Matthew
Date of Award: 2020
Depositing User: Dr Jake Casson
Unique ID: glathesis:2020-80297
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 31 Mar 2020 10:46
Last Modified: 31 Mar 2020 10:47
Thesis DOI: 10.5525/gla.thesis.80297
URI: http://theses.gla.ac.uk/id/eprint/80297
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