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CHARACTERIZATION OF THE BONE MICROENVIRONMENT CELL COMPOSITION IN OVARIAN CANCER

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abstract
Despite rates for new ovarian cancer cases and ovarian cancer death rates dropping on average 2.3% each year over the last 10 years, ovarian cancer accounts for more deaths than any other gynecological malignancies. Ovarian cancer rates are highest in women aged 55-64 with 80% of diagnoses presenting with regional or distant metastases. Although, only 1% of ovarian cancer patients will be diagnosed with clinically relevant bone metastases but postmortem autopsies reveal an incidence rate of nearly 10%. The unique characteristics of ovarian cancer metastasis have been well described, however the mechanism of distant bone metastasis is still poorly understood due to the low clinical incidence rate. In this study, we established a multi-flurochrome bone marrow cell-typing methodology and used it to characterize changes in the bone niche with ovarian cancer growth and osteoarthritis. We found that tumor growth reduces the numbers of hematopoietic stem cells and increases osteopontin expression in the osteoarthritic bone niche. Furthermore, we demonstrated osteoclast and MSC numbers increase and subsequent osteoclastic bone reabsorption also increases in the arthritic bone microenvironment with ovarian tumor growth. These findings provide methodologies to investigate bone micro-environmental alterations with disease incidence and demonstrate ovarian tumor induced remodeling and subsequent HSC and MSC mobilization away from the osteoarthritic bone niche.
subject
Bone Metastasis
Cancer Biology
Microenvironment
Osteoarthritis
Ovarian Cancer
Tissue Remodeling
contributor
Patel, Chirayu (author)
Kerr, Bethany A (committee chair)
Tsang, Allen W (committee member)
Willey, Jeff S (committee member)
date
2020-01-08T09:35:25Z (accessioned)
2021-01-07T09:30:18Z (available)
2020 (issued)
degree
Biomedical Science – MS (discipline)
embargo
2021-01-07 (terms)
identifier
http://hdl.handle.net/10339/95954 (uri)
language
en (iso)
publisher
Wake Forest University
title
CHARACTERIZATION OF THE BONE MICROENVIRONMENT CELL COMPOSITION IN OVARIAN CANCER
type
Thesis

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