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ANGIOTENSIN II: THE EFFECT ON PROSTATE CANCER CELL PROLIFERATION, NERVE SPROUTING, AND CANCER INDUCED BONE PAIN

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title
ANGIOTENSIN II: THE EFFECT ON PROSTATE CANCER CELL PROLIFERATION, NERVE SPROUTING, AND CANCER INDUCED BONE PAIN
author
Contino, Kelly Frances
abstract
BACKGROUND: Up to 90% of patients who die from prostate cancer have bone metastasis, accompanied by debilitating pain. Why prostate cancer preferentially metastasizes to bone is unknown. Evidence suggests tumor cells compete for space in bone marrow through mechanisms similar to hematopoietic stem cells (HSCs). Nerve fibers, involved in HSC homing, may also be involved in tumor progression to bone marrow. The renin-angiotensin system (RAS), involved in nerve sprouting and tumor proliferation, may facilitate crosstalk between nerves and tumor cells. This study sought to explore mechanisms through which RAS effects bone metastatic progression and pain. RESULTS/CONCLUSIONS: Genomic analysis found that Angiotensinogen (AGT) is elevated in metastatic prostate cancer. Metastatic prostate cancer cells, C4-2B and DU145 were found to express the highest and lowest AGT respectively. AGT was then knocked-down (KD) in each. The KD significantly decreased proliferation in tumor cells. When cells were treated with ACE inhibitor captopril, proliferation stayed consistent. However, nerve sprouting decreased significantly in primary dorsal root ganglia (DRG) neuronal cells following treatment with AGT KD conditioned media. Further experimentation revealed that treatment with Ang II induced sprouting in primary neuronal DRG cells. Results suggest that nerve sprouting and prostate cancer proliferation are influenced by the RAS.
subject
Angiotensin II
Bone Metastasis
Cancer Proliferation
Nerve Sprouting
Prostate Cancer
contributor
Shiozawa, Yusuke (committee chair)
Singh, Ravi (committee member)
date
2022-05-24T08:35:51Z (accessioned)
2022 (issued)
degree
Biomedical Science – MS (discipline)
embargo
2024-05-23 (terms)
2024-05-23 (liftdate)
identifier
http://hdl.handle.net/10339/100720 (uri)
language
en (iso)
publisher
Wake Forest University
type
Thesis

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