The Role of CD24 in Human Bladder Cancer Tumorigenesis and Metastasis Progression

Overdevest, Jonathan Brett, Department of Molecular Physiology and Biological Physics, University of Virginia
Theodorescu, Dan, Department of Molecular Physiology and Biological Physics, University of Virginia
Wamhoff, Brian
Mandell, James, Department of Pathology, University of Virginia
Kelly, Kimberly, Department of Biomedical Engineering, University of Virginia
Moskaluk, Christopher, Department of Pathology, University of Virginia

Expression of CD24, a GPI-linked sialoglycoprotein and cancer stem cell marker, is associated with metastatic progression in multiple cancer types, yet the functionality of CD24 in this process remains unclear. We have previously demonstrated that CD24 is a key contributor to in vitro tumor cell proliferation and anchorage independent growth. Meanwhile, other reports have suggested that tumor cells expressing CD24 bind to P-selectin on activated platelets and endothelial cells. Although insightful, CD24 is widely believed to have additional functionality due to its widespread presence in primary tumors, profound correlation with metastatic development and prognostic capability in patients. Thus, we sought to investigate whether CD24 is simply an excellent biomarker in cancer or if it serves a functionally critical role in tumorigenesis and metastasis We also wanted to evaluate the kinetics of CDs invlovement in these processes using both carcinogenesis to induce urothelial tumors for early stage disease assessment, as well as a bioluminescent experimental model of metastasis for monitoring disease progression. Finally, we hoped to analyze metastases from human bladder cancer patients for CD24 expression, and if present, probe the efficacy of anti-CD24 monoclonal antibody in curtailing metastatic proliferation. Herein, we address these deficiencies in an effort to understand the role of CD24 in bladder tumorigenesis and metastatic progression.

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PHD (Doctor of Philosophy)
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