Exploring the role of obesity in prostate cancer progression and metastasis with organoid system
Author(s)
Dai, Zhonghao
Advisor(s)
Editor(s)
Collections
Supplementary to:
Permanent Link
Abstract
Epidemiological studies suggest that obese individuals with prostate cancer are at an increased risk of disease recurrence, earlier progression, and development of metastatic disease, although the exact mechanisms remain relatively obscure. Thus, understanding the mechanisms by which obesity promotes the incidence or aggressiveness of cancer may lead to new strategies to prevent and treat the disease. In our studies, we developed a synthetic polymer-based, hydrogel platform of maleimide-functionalized 4-arm poly(ethylene glycol) (PEG-4MAL) to grow prostate cancer cells under the defined extracellular matrix (ECM) microenvironment, and established prostate cancer organoid representing both standard and obese-mimic conditions through controlled media supplementation. Here, we demonstrated that prostate cancer organoids treated with obesity-mimic media show a higher proliferation potential, upregulation of transmembrane fatty acid transporter protein CD36, elevated levels of cancer stem cell (CSC) biomarkers, phenotypical switch toward mesenchymal states with increased metastatic potential, and become more resistant to standardized anti-androgen therapy. We also demonstrate ECM-dependent response to obesity media supplementation in all of the aspects described above, which suggests interplays between the ECM-integrin signaling with the alteration of metabolism induced by obesity. This synthetic hydrogel platform can provide a more defined microenvironment to study the obesity-induced prostate cancer progression and can be potentially used for drug discovery.
Sponsor
Date
2022-05-03
Extent
Resource Type
Text
Resource Subtype
Thesis