Modeling and Intervening in Pathologic Interactions of Platelets and Ovarian Cancer
Ovarian cancer and platelets promote each other in a pathologic feedforward loop which result in poor prognosis of cancer, thrombosis and death as a result. The goals of this dissertation were to: i) evaluate the interaction between ovarian cancer cells and platelets using healthy or cancer patient-...
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| Format | Dissertation |
| Language | English |
| Published |
ProQuest Dissertations & Theses
01.01.2022
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| Online Access | Get full text |
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| Summary: | Ovarian cancer and platelets promote each other in a pathologic feedforward loop which result in poor prognosis of cancer, thrombosis and death as a result. The goals of this dissertation were to: i) evaluate the interaction between ovarian cancer cells and platelets using healthy or cancer patient-derived platelets, and ii) evaluate the potential of platelet inhibitors for prevention of ovarian cancer tumor establishment and progression in vivo using orthotopic ovarian mouse-models.We hypothesized that: 1) the biology of platelets and their aggregation capabilities are different in patients with ovarian cancer compared to healthy controls, and 2) platelet inhibitors reduce platelet-mediated effects on ovarian cancer in vitro and in vivo. To test these hypotheses, we collected blood from healthy controls and ovarian cancer patients to evaluate platelets differences between the two groups. We also developed a spheroid and ovarian cancer mouse-models to test the effect of platelets inhibitors on ovarian cancer and platelets interactions.Our findings identified that alterations in platelet biology, and not just increased platelet numbers, in ovarian cancer patients contributes to the increased platelet aggregation in blood from ovarian cancer patients. The in vitro results identified the liver X receptor (LXR)/retinoid X receptor (RXR) and integrin signaling pathways as candidate mediators of ovarian cancer thrombosis and metastasis. The in vivo results suggested that platelet exposure decreases ovarian cancer liver metastases and that a platelet inhibitor reduces this effect. These data will be used to a design future research evaluating the role of platelets in liver metastasis, and test LXR/RXR and integrin signaling as potential targetable pathways for interfering with ovarian cancer related thrombosis and metastasis |
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| ISBN: | 9798368477497 |