Dissertation
The role of interleukin-1 beta in metastatic colonization of prostate cancer cells
Doctor of Philosophy (Ph.D.), Drexel University
Jun 2020
DOI:
https://doi.org/10.17918/00000029
Abstract
Metastatic Prostate Cancer (mPCa) presents a 5-year survival rate of 29% and is currently incurable. Previous work from our group determined that skeletal metastases in PCa patients contain approximately 35% of tumor cells lacking the Androgen Receptor (AR), a nuclear receptor considered the major driver of this disease. Additionally, we revealed that Interleukin-1beta (IL-1[beta]) is exclusively expressed in ARNeg PCa cells and the expression of this cytokine promotes metastatic behavior of PCa cells in animal models by conditioning, cells from the bone stroma, facilitating colonization and tumor growth in the skeleton. In the context of metastasis, cancer cells need to adapt to the tissue microenvironment of targeted organs. This process may involve the conditioning of the newly found stroma starting immediately after the arrival of cancer cells to secondary sites. In vitro and in vivo studies confirmed that 1. IL-1[beta] directly regulates expression of chemokine ligand 5 (CCL5) and cyclooxygenase 2 (COX-2), by an NF-[kappa]B-independent mechanism in bone stromal cells 2. CCL5 signals through the CCR5 receptor in PCa cells. The overexpression of this receptor significantly enhances survival of ARNeg PCa cells in the bone. These studies elucidate the role of IL-1[beta] in the conditioning of the stroma by upregulating tumor associated genes in bone stroma cells shifting the current treatment paradigms towards therapeutic targeting of ARNeg cells in combination with the current standard of care.
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Details
- Title
- The role of interleukin-1 beta in metastatic colonization of prostate cancer cells
- Creators
- Melisa Diaz
- Contributors
- Alessandro Fatatis (Advisor)
- Awarding Institution
- Drexel University
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Number of pages
- ix, 107 pages
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems (1997-2026); Drexel University
- Other Identifier
- 991014695248104721