Effect of Matrix Alignment and Substrate Stiffness on Migration of Heterogenous Myoferlin Depleted Breast Cancer Cell Populations
Keywords:Epithelial to Mesenchymal Transition
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Publisher:The Ohio State University
Series/Report no.:The Ohio State University. Department of Biomedical Engineering Honors Theses; 2019
Breast cancer is the second leading cause of cancer death in women (NBCF, 2019). Of all potential breast cancers, 10-20% are triple negative, which tend to be more aggressive than other breast cancer types ("Breastcancer.org - Breast Cancer Information and Support," 2019). Aggressive breast cancer is defined by the cancers ability to metastasize and spread to other parts of the breast. Myoferlin (MYOF), a protein that promotes cell motility and plasma membrane repair is reported at higher levels in breast cancer cells compared to normal tissue and previous studies by our group have observed the effect of removing or knocking down MYOF (MYOF-KD or KD) expression in the MDA-MB-231 cell line (Li et al., 2012). These studies indicated MYOFKD lead to Mesenchymal to Epithelial Transition (MET) in the MDA-MB-231 cells, leading to phenotypical and migratory changes promoting less aggressive behavior (Volakis et al., 2014). Although structural remodeling of the tumor microenvironment (TME) is known to facilitate cell migration, it is not known if these structural cues alter the migratory phenotype of MYOF-KD cells (Levental et al., 2009). Furthermore, it is not known how the presence of mixed cell populations (parental wild-type and MYOFKD) alters overall cell migration. Therefore, in this study we will investigate how structural cues and intercellular interactions between MYOFKD and parental wild-type (WT) cells influence cell migration behavior. For migratory experiments, patterned PDMS with rectilinear structure substrates will be prepared using soft lithography techniques. Additionally, aligned polyacrylamide gels were prepared with various stiffness. Cells will be labeled with lipophilic tracers to track migration with 24-hour time-lapse fluorescent microscopy. Cells will be seeded to form a rectangular monolayer or 3D tumor spheroids for migration.
Academic Major: Biomedical Engineering
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