Fluid Force Alterations in Cultured Mammary Epithelial and Breast Cancer Cells: Applications in Breast Cancer Diagnosis

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atmire.migration.oldid5016
dc.contributor.advisorRinker, Kristina
dc.contributor.authorFuh, Kenneth Fuh
dc.contributor.committeememberShemanko, Carrie
dc.contributor.committeememberKallos, Michael
dc.contributor.committeememberUngrin, Mark
dc.contributor.committeememberWang, Edwin
dc.contributor.committeememberLeask, Richard
dc.date.accessioned2016-10-11T15:29:52Z
dc.date.available2016-10-11T15:29:52Z
dc.date.issued2016
dc.date.submitted2016en
dc.description.abstractMetastatic progression of breast cancer is characterized by mechanical interactions between tumor cells and various microenvironments, including exposure to fluid flow. Complementing genomic and molecular signaling studies with fluid mechanics holds the promise of providing in-depth knowledge into how these interactions affect the ability of tumor cells to undergo metastasis, and identification of novel biomarkers that can potentially facilitate breast cancer diagnosis and treatment. In this thesis, a bioreactor system was used to expose cultured mammary epithelial and breast cancer cells to fluid shear stress in the physiological range of those experienced in the vascular microenvironment. Genome-wide expression analysis revealed an effect of fluid flow on gene expression patterns and cellular processes involved in metastasis such as EMT, cell migration and adhesion. In addition, TGF-β signaling activity was significantly enriched and several genes belonging to this pathway were overexpressed upon flow exposure. Subsequently, we sought to identify novel flow-responsive biomarkers for breast cancer. For this purpose, bioinformatics and network biology approaches were used to reveal significant enrichment of biological processes involved in metastatic progression. Expression levels of differentially expressed genes were evaluated in clinical expression datasets, and 14 genes were identified as potential biomarkers. Relative expression levels of seven of these biomarkers were quantified in breast cancer patients and healthy volunteers. Five biomarkers passed the threshold for statistical significance and were overexpressed in more than 80% of patients presenting with basal and HER2-enriched breast cancers, which are the most aggressive subtypes of breast cancer. To our knowledge, the studies presented herein are the first of their kind to demonstrate that using an in vitro model to simulate exposure of cells to fluid shear stresses allows for identification of biomarkers for breast cancer. Using this system to study cellular events involved in other types of cancers may lead to new diagnostic and therapeutic approaches for metastatic cancer progression.en_US
dc.identifier.citationFuh, K. F. (2016). Fluid Force Alterations in Cultured Mammary Epithelial and Breast Cancer Cells: Applications in Breast Cancer Diagnosis (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/26197en_US
dc.identifier.doihttp://dx.doi.org/10.11575/PRISM/26197
dc.identifier.urihttp://hdl.handle.net/11023/3419
dc.language.isoeng
dc.publisher.facultyGraduate Studies
dc.publisher.institutionUniversity of Calgaryen
dc.publisher.placeCalgaryen
dc.rightsUniversity of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.
dc.subjectBioinformatics
dc.subjectBiology--Cell
dc.subjectBiology--Molecular
dc.subjectOncology
dc.subjectEngineering--Biomedical
dc.subject.classificationbreast canceren_US
dc.subject.classificationdiagnosticsen_US
dc.subject.classificationmetastasisen_US
dc.subject.classificationBiomarkersen_US
dc.subject.classificationfluid flowen_US
dc.titleFluid Force Alterations in Cultured Mammary Epithelial and Breast Cancer Cells: Applications in Breast Cancer Diagnosis
dc.typedoctoral thesis
thesis.degree.disciplineBiomedical Engineering
thesis.degree.grantorUniversity of Calgary
thesis.degree.nameDoctor of Philosophy (PhD)
ucalgary.item.requestcopytrue
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