Item Details

title

THE ROLE OF PROSTATE CANCER IN THE BONE MICROENVIRONMENT AND ITS IMPLICATION IN CANCER INDUCED BONE PAIN

author

Ollodart, Jenna

abstract

Prostate cancer (PCa) bone metastasis is incurable, but currently only few successful therapies exist. Many late stage PCa patients develop bone metastasis and have increased expression of cyclin-dependent-kinase-8/19 (CDK8/19). In this study, we determined whether the inhibition of CDK8/19 can attenuate PCa bone metastatic growth. We found CDK8/19 inhibition can attenuate bone metastatic progression in osteolytic PCa but not osteoblastic PCa. Bone metastasis is not only incurable but also painful. The cancer-induced bone pain (CIBP) impairs patients’ quality of life. However, current treatments for CIBP are associated with adverse effects and inadequately manage the. To create more effective and safer therapies for CIBP, we first must understand the underlying mechanisms. To do so, the molecular interactions between bone metastatic cells and the bone marrow microenvironment were examined through single-cell RNA sequencing (scRNAseq). In the mice intrafemorally inoculated with the murine PCa, RM1-2H9, through scRNAseq we found an increased fibroblast population compared to other PCa inoculated. Furthermore, these fibroblasts also expressed markers associated with nociception. Taken together, our findings suggest (i) that CDK8/19 inhibition can be a treatment for osteolytic PCa bone metastasis, and (ii) that bone marrow cancer-associated fibroblasts may be involved in CIBP development.

subject

Bone Metastasis

Cancer-induced bone pain

CDK8/19

Prostate Cancer

scRNAseq

contributor

Shiozawa, Yusuke (advisor)

Peters, Christopher (committee member)

Miller, Lance (committee member)

date

2023-07-25T17:48:37Z (accessioned)

2023 (issued)

degree

Biomedical Science – MS (discipline)

embargo

2028-05-13 (terms)

2028-05-13 (liftdate)

identifier

http://hdl.handle.net/10339/102247 (uri)

language

en (iso)

publisher

Wake Forest University

type

Thesis