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Establishing the Effects of Adipose Derived Stem Cells (ADSCs) on the Tumorigenic Characteristics of Breast Cancer / EMMAN THOMSON

Swansea University Author: EMMAN THOMSON

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DOI (Published version): 10.23889/SUthesis.62321

Abstract

Introduction: Breast Cancer affects approximately 55,000 women in the UK every year, with the majority (>70%) being oestrogen receptor (ER) positive. Advancements in screening, imaging and adjuvant therapies mean more women are diagnosed earlier and undergo breast-conserving surgery (BCS). There...

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Published: Swansea 2022
Institution: Swansea University
Degree level: Doctoral
Degree name: Ph.D
Supervisor: Doak, Shareen; Whitaker, Iain
URI: https://cronfa.swan.ac.uk/Record/cronfa62321
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fullrecord <?xml version="1.0" encoding="utf-8"?><rfc1807 xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:xsd="http://www.w3.org/2001/XMLSchema"><bib-version>v2</bib-version><id>62321</id><entry>2023-01-13</entry><title>Establishing the Effects of Adipose Derived Stem Cells (ADSCs) on the Tumorigenic Characteristics of Breast Cancer</title><swanseaauthors><author><sid>3e88b690a1d0d1f4f90baa4463461080</sid><firstname>EMMAN</firstname><surname>THOMSON</surname><name>EMMAN THOMSON</name><active>true</active><ethesisStudent>false</ethesisStudent></author></swanseaauthors><date>2023-01-13</date><abstract>Introduction: Breast Cancer affects approximately 55,000 women in the UK every year, with the majority (&gt;70%) being oestrogen receptor (ER) positive. Advancements in screening, imaging and adjuvant therapies mean more women are diagnosed earlier and undergo breast-conserving surgery (BCS). There has been a resultant rise in the use of free fat transfer (FFT) to reconstruct the small to medium volume loss, utilising autologous adipose tissue. Contemporary scientific studies demonstrate that co-location of breast cancer and adipose derived stem cells (ADSCs) present in FFT, results in the conference of a malignant advantage via cytokine release and co-located cell-to-cell interaction. As these studies predominantly utilise ADSCs isolated from healthy patients, there is a limit to how these results apply to the clinical patient group of women with breast cancer. This thesis aimed to create, for the first time, a clinically representative model by isolating ADSCs from women with breast cancer undergoing systemic treatment. Thus establishing if patient selection plays a role in the effects imparted by ADSCs upon the functional and phenotypic characteristics associated with the cancer hallmarks. Methods: An optimised ADSC isolation protocol produced a reliable cell population for the study duration. ADSCs harvested from patients with (n=10) and without breast cancer (n=6) were isolated and fully characterised using the Dominici criteria for stem cells. Conditioned media (CM) and non-contact co-culture models were applied to examine the effect that ADSCs isolated from breast cancer patients had on the neoplastic traits of MCF-7 and T47D ER+ breast cancer cell lines when compared with their healthy counterparts. Experiments were designed to measure a range of functional and morphological endpoints, related to the cancer hallmarks. This included proliferation, changes in cellular adhesion and migration, invasion, cellular and nuclei morphology, protein expression and bioenergetics. Results: Successfully isolated ADSCs demonstrated plastic adherence, trilineage differentiation and appropriate cell surface markers as confirmed using flow cytometry. Data showed statistically significant increases (p&lt;0.05) in proliferation and invasion only when MCF-7 cells were treated with media conditioned by ADSCs from healthy patients. Significant increases in migration and invasion, with reduction in adhesion and raised concentrations of cytokines (IL-6, VEG-F and MCP-1) was only seen when MCF-7 cells were co-cultured with ADSCs isolated from healthy patients. There was a lack of effect seen in both CM and co-culture experiments involving ADSCs isolated from cancer patients, a novel finding, as this patient group had not previously been a focus of study. Similar results were seen in the second ER+ cell line (T47D) which was used for experimental validation, with increases in proliferation, invasion, and an increase in abnormal metabolic activity when co-cultured with healthy ADSCs only. Conclusion: Utilising a novel approach to patient selection, it has been possible to show a divergence in the behaviour of ADSCs isolated from patients with breast cancer undergoing systemic treatment, when compared with ADSCs isolated from healthy patients. This study presents a two-part cell-based model which more accurately represents the clinical population undergoing FFT. 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spelling v2 62321 2023-01-13 Establishing the Effects of Adipose Derived Stem Cells (ADSCs) on the Tumorigenic Characteristics of Breast Cancer 3e88b690a1d0d1f4f90baa4463461080 EMMAN THOMSON EMMAN THOMSON true false 2023-01-13 Introduction: Breast Cancer affects approximately 55,000 women in the UK every year, with the majority (>70%) being oestrogen receptor (ER) positive. Advancements in screening, imaging and adjuvant therapies mean more women are diagnosed earlier and undergo breast-conserving surgery (BCS). There has been a resultant rise in the use of free fat transfer (FFT) to reconstruct the small to medium volume loss, utilising autologous adipose tissue. Contemporary scientific studies demonstrate that co-location of breast cancer and adipose derived stem cells (ADSCs) present in FFT, results in the conference of a malignant advantage via cytokine release and co-located cell-to-cell interaction. As these studies predominantly utilise ADSCs isolated from healthy patients, there is a limit to how these results apply to the clinical patient group of women with breast cancer. This thesis aimed to create, for the first time, a clinically representative model by isolating ADSCs from women with breast cancer undergoing systemic treatment. Thus establishing if patient selection plays a role in the effects imparted by ADSCs upon the functional and phenotypic characteristics associated with the cancer hallmarks. Methods: An optimised ADSC isolation protocol produced a reliable cell population for the study duration. ADSCs harvested from patients with (n=10) and without breast cancer (n=6) were isolated and fully characterised using the Dominici criteria for stem cells. Conditioned media (CM) and non-contact co-culture models were applied to examine the effect that ADSCs isolated from breast cancer patients had on the neoplastic traits of MCF-7 and T47D ER+ breast cancer cell lines when compared with their healthy counterparts. Experiments were designed to measure a range of functional and morphological endpoints, related to the cancer hallmarks. This included proliferation, changes in cellular adhesion and migration, invasion, cellular and nuclei morphology, protein expression and bioenergetics. Results: Successfully isolated ADSCs demonstrated plastic adherence, trilineage differentiation and appropriate cell surface markers as confirmed using flow cytometry. Data showed statistically significant increases (p<0.05) in proliferation and invasion only when MCF-7 cells were treated with media conditioned by ADSCs from healthy patients. Significant increases in migration and invasion, with reduction in adhesion and raised concentrations of cytokines (IL-6, VEG-F and MCP-1) was only seen when MCF-7 cells were co-cultured with ADSCs isolated from healthy patients. There was a lack of effect seen in both CM and co-culture experiments involving ADSCs isolated from cancer patients, a novel finding, as this patient group had not previously been a focus of study. Similar results were seen in the second ER+ cell line (T47D) which was used for experimental validation, with increases in proliferation, invasion, and an increase in abnormal metabolic activity when co-cultured with healthy ADSCs only. Conclusion: Utilising a novel approach to patient selection, it has been possible to show a divergence in the behaviour of ADSCs isolated from patients with breast cancer undergoing systemic treatment, when compared with ADSCs isolated from healthy patients. This study presents a two-part cell-based model which more accurately represents the clinical population undergoing FFT. This study recommends an alternative patient group (women with cancer on systemic treatment) as the primary cell source for research examining ADSC behaviour in the breast cancer micro-environment. E-Thesis Swansea Adipose Derived Stem Cell, ADSC, Breast Cancer, Lipofilling 21 12 2022 2022-12-21 10.23889/SUthesis.62321 COLLEGE NANME COLLEGE CODE Swansea University Doak, Shareen; Whitaker, Iain Doctoral Ph.D RCSEng, WCAT 2024-02-14T12:39:13.2056581 2023-01-13T12:46:24.8430616 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Medicine EMMAN THOMSON 1 62321__26285__b5074950b7aa49a7848ab7694aaa0899.pdf Thomson_Emman_PhD_Thesis_Final_Embargoed_Redacted_Signature.pdf 2023-01-13T13:10:10.2000165 Output 29003967 application/pdf E-Thesis – open access true 2023-12-21T00:00:00.0000000 Copyright: The author, Emman Thomson, 2022. Released under the terms of a Creative Commons Attribution-Only (CC-BY) License. Third party content is excluded for use under the license terms. true eng https://creativecommons.org/licenses/by/4.0/
title Establishing the Effects of Adipose Derived Stem Cells (ADSCs) on the Tumorigenic Characteristics of Breast Cancer
spellingShingle Establishing the Effects of Adipose Derived Stem Cells (ADSCs) on the Tumorigenic Characteristics of Breast Cancer
EMMAN THOMSON
title_short Establishing the Effects of Adipose Derived Stem Cells (ADSCs) on the Tumorigenic Characteristics of Breast Cancer
title_full Establishing the Effects of Adipose Derived Stem Cells (ADSCs) on the Tumorigenic Characteristics of Breast Cancer
title_fullStr Establishing the Effects of Adipose Derived Stem Cells (ADSCs) on the Tumorigenic Characteristics of Breast Cancer
title_full_unstemmed Establishing the Effects of Adipose Derived Stem Cells (ADSCs) on the Tumorigenic Characteristics of Breast Cancer
title_sort Establishing the Effects of Adipose Derived Stem Cells (ADSCs) on the Tumorigenic Characteristics of Breast Cancer
author_id_str_mv 3e88b690a1d0d1f4f90baa4463461080
author_id_fullname_str_mv 3e88b690a1d0d1f4f90baa4463461080_***_EMMAN THOMSON
author EMMAN THOMSON
author2 EMMAN THOMSON
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publishDate 2022
institution Swansea University
doi_str_mv 10.23889/SUthesis.62321
college_str Faculty of Medicine, Health and Life Sciences
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hierarchy_top_id facultyofmedicinehealthandlifesciences
hierarchy_top_title Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id facultyofmedicinehealthandlifesciences
hierarchy_parent_title Faculty of Medicine, Health and Life Sciences
department_str Swansea University Medical School - Medicine{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Medicine
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description Introduction: Breast Cancer affects approximately 55,000 women in the UK every year, with the majority (>70%) being oestrogen receptor (ER) positive. Advancements in screening, imaging and adjuvant therapies mean more women are diagnosed earlier and undergo breast-conserving surgery (BCS). There has been a resultant rise in the use of free fat transfer (FFT) to reconstruct the small to medium volume loss, utilising autologous adipose tissue. Contemporary scientific studies demonstrate that co-location of breast cancer and adipose derived stem cells (ADSCs) present in FFT, results in the conference of a malignant advantage via cytokine release and co-located cell-to-cell interaction. As these studies predominantly utilise ADSCs isolated from healthy patients, there is a limit to how these results apply to the clinical patient group of women with breast cancer. This thesis aimed to create, for the first time, a clinically representative model by isolating ADSCs from women with breast cancer undergoing systemic treatment. Thus establishing if patient selection plays a role in the effects imparted by ADSCs upon the functional and phenotypic characteristics associated with the cancer hallmarks. Methods: An optimised ADSC isolation protocol produced a reliable cell population for the study duration. ADSCs harvested from patients with (n=10) and without breast cancer (n=6) were isolated and fully characterised using the Dominici criteria for stem cells. Conditioned media (CM) and non-contact co-culture models were applied to examine the effect that ADSCs isolated from breast cancer patients had on the neoplastic traits of MCF-7 and T47D ER+ breast cancer cell lines when compared with their healthy counterparts. Experiments were designed to measure a range of functional and morphological endpoints, related to the cancer hallmarks. This included proliferation, changes in cellular adhesion and migration, invasion, cellular and nuclei morphology, protein expression and bioenergetics. Results: Successfully isolated ADSCs demonstrated plastic adherence, trilineage differentiation and appropriate cell surface markers as confirmed using flow cytometry. Data showed statistically significant increases (p<0.05) in proliferation and invasion only when MCF-7 cells were treated with media conditioned by ADSCs from healthy patients. Significant increases in migration and invasion, with reduction in adhesion and raised concentrations of cytokines (IL-6, VEG-F and MCP-1) was only seen when MCF-7 cells were co-cultured with ADSCs isolated from healthy patients. There was a lack of effect seen in both CM and co-culture experiments involving ADSCs isolated from cancer patients, a novel finding, as this patient group had not previously been a focus of study. Similar results were seen in the second ER+ cell line (T47D) which was used for experimental validation, with increases in proliferation, invasion, and an increase in abnormal metabolic activity when co-cultured with healthy ADSCs only. Conclusion: Utilising a novel approach to patient selection, it has been possible to show a divergence in the behaviour of ADSCs isolated from patients with breast cancer undergoing systemic treatment, when compared with ADSCs isolated from healthy patients. This study presents a two-part cell-based model which more accurately represents the clinical population undergoing FFT. This study recommends an alternative patient group (women with cancer on systemic treatment) as the primary cell source for research examining ADSC behaviour in the breast cancer micro-environment.
published_date 2022-12-21T12:39:12Z
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