Item Details

title

CHARACTERIZATION OF THE BONE MICROENVIRONMENT CELL COMPOSITION IN OVARIAN CANCER

author

Patel, Chirayu

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

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

type

Thesis