Thesis
CX3CR1 regulation and signaling during phenotypic plasticity of prostate cancer cells
Master of Science (M.S.), Drexel University
Aug 2023
DOI:
https://doi.org/10.17918/00001817
Abstract
Prostate cancer (PCa) is one of the most frequently diagnosed malignancies amongst men in the United States, with approximately 300,000 new cases each year. While 5-year survival for locally confined tumors are high, around 20 percent of patients will eventually undergo metastatic recurrence. Metastasis is incurable and results in upwards of 90 percent of cancer-related deaths. Recent studies have revealed an emerging role of cancer stem cells (CSCs) in this process. CSCs are able to divide asymmetrically, generating a new CSC as well as a differentiated cell, thus, allowing for population maintenance. CSCs are inherently resistant to therapies and able to colonize secondary organs, sustaining growth and starting metastasis. CSCs are supported in completing these tasks by the tumor microenvironment. Our lab has identified subsets of tumor cells that highly express CX3CR1, a chemokine receptor, denoted CX3CR1high cells. CX3CR1high express stemness markers in combination with the pluripotency genes Oct4a and Nanog, and are endowed with metastasis-initiating capabilities. On the other hand, CX3CR1low cells are capable of undergoing phenotypic plasticity - both in vitro and in vivo by re-expressing CX3CR1 on the surface while concurrently increasing pluripotency markers. In the present study, we examined the expression levels of the four CX3CR1 transcriptional variants and two protein isoforms in PCa cells and cells undergoing phenotypic plasticity. Next, we assessed the effects on CX3CR1 expression exerted by the reduced oxygen levels commonly observed in the bone marrow, to assess the potential role of this microenvironment in modulating CX3CR1 (re)expression in skeletal metastasis. Finally, we investigated the role of the signaling molecule Wnt11 in activating the ROR2 receptor in prostate cancer cells, as a means of communication between osteoblasts and prostate cancer cells.
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Details
- Title
- CX3CR1 regulation and signaling during phenotypic plasticity of prostate cancer cells
- Creators
- Jennifer Lynch
- Contributors
- Gabriele Romano (Advisor)Alessandro Fatatis (Advisor)
- Awarding Institution
- Drexel University
- Degree Awarded
- Master of Science (M.S.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Number of pages
- viii, 63 pages
- Resource Type
- Thesis
- Language
- English
- Academic Unit
- Medicine (Graduate); College of Medicine; Hematology and Oncology; Drexel University
- Other Identifier
- 991021229815004721