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dc.contributor.authorLiu, Luen_US
dc.date.accessioned2017-01-11T09:00:29Z
dc.date.available2017-01-11T09:00:29Z
dc.date.issued2017-01-10en_US
dc.identifier.othervt_gsexam:9486en_US
dc.identifier.urihttp://hdl.handle.net/10919/74235
dc.description.abstractEpithelial ovarian cancer (EOC) is the leading cause of death from gynecological malignancy due to the insufficient accurate screening programs for the early detection of EOC. To improve the accuracy of the early detection, there is a need to deeply understand the mechanism of EOC progression and the interaction between cancer cells with their unique microenvironment. Therefore, this work investigated the metabolic shift in the mouse model for progressive ovarian cancer, and evaluated the effects of hypoxic environment, spheroid formation as well as stromal vascular fractions (SVF) on the metabolic shift, proliferation rate, drug resistance and protein markers in functional categories. The results demonstrated an increasingly glycolytic nature of MOSE cells as they progress from a tumorigenic (MOSE-L) to a highly aggressive phenotype (MOSE-FFL), and also showed changes in metabolism during ovarian cancer spheroid formation with SVF under different oxygen levels. More specifically, the hypoxic environment enhanced glycolytic shift by upregulating the glucose uptake and lactate secretion, and the spheroid formation affected the cellular metabolism by increasing the lactate secretion to acidify local environments, modulating the expression of cell adhesion molecules to enhance cell motility and spheroids disaggregation, and up-regulating invasiveness markers and stemness makers to promote ovarian cancer aggressive potential. Hypoxia and spheroid formation decreased ovarian cancer cells growth but increased the chemoresistance, which leads to the promotion of aggressiveness and metastasis potential of ovarian cancer. SVF co-cultured spheroids further increased the glycolytic shift of the heterogeneous of ovarian cancer spheroids, induced the aggressive phenotype by elevating the corresponding protein markers. Decreasing the glycolytic shift and suppression of the proteins/pathways may be used to inhibit aggressiveness or metastatic potential of ovarian cancer heterogeneous of ovarian cancer spheroids, induced the aggressive phenotype by elevating the corresponding protein markers. Decreasing the glycolytic shift and suppression of the proteins/pathways may be used to inhibit aggressiveness or metastatic potential of ovarian cancer.en_US
dc.format.mediumETDen_US
dc.publisherVirginia Techen_US
dc.rightsIn Copyrighten
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/en
dc.subjectovarian canceren_US
dc.subjectmetabolismen_US
dc.subjecthypoxiaen_US
dc.subjectspheroidsen_US
dc.subjectstromal vascular fractionsen_US
dc.subjectinvasivenessen_US
dc.titleThe effect of hypoxia and 3D culture conditions on heterogeneous ovarian cancer spheroidsen_US
dc.typeThesisen_US
dc.contributor.departmentHuman Nutrition, Foods, and Exerciseen_US
dc.description.degreeMaster of Scienceen_US
thesis.degree.nameMaster of Scienceen_US
thesis.degree.levelmastersen_US
thesis.degree.grantorVirginia Polytechnic Institute and State Universityen_US
thesis.degree.disciplineHuman Nutrition, Foods, and Exerciseen_US
dc.contributor.committeechairSchmelz, Eva M.en_US
dc.contributor.committeememberHuckle, William R.en_US
dc.contributor.committeememberFrisard, Madlyn I.en_US


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