Date of Award
Master of Science
Jennifer A. Doll
Jeri-Annette Lyons, Dean Nardelli, Janis Eells
Biomedical Sciences, Prostate Cancer
Background: Prostate cancer (PCa) is a leading men's health concern. It is the most common cancer diagnosed in American men. Obesity, especially excess visceral adipose tissue, increases the risk of PCa progression; however, the mechanism is yet unknown. In addition, studies have demonstrated that the locale of the visceral adipose depots affects its function and change the levels of secreted products. In PCa patients, increased thickness of the periprostatic adipose tissue (PPA), a type of visceral adipose tissue which covers the prostate organ, is positively correlated with progression, suggesting that this depot may specifically stimulate PCa progression in obese patients. In this study, I tested the hypothesis that visceral adipose tissue (VAT) secretions, and specifically PPA tissue secretions, from a mouse model will induce pro-proliferative activity of microvascular endothelial and PCa cells. This hypothesis was tested by two aims. The first was quantifying the pro-proliferative activity of subcutaneous (SQA) and VAT secretions on normal human endothelial cells. The second aim was to measure the proproliferative activity of adipose tissue secretions on PC-3 PCa cells.
Method: SQA and two types of VAT, including visceral fat pad (VFP), and PPA tissues from wildtype mice C57BI/6 and obese mice were collected. Tissues were minced and placed in explant cultures in serum-free media. Conditioned media (CM) was collected after 48 hours of incubation. Human microvascular endothelial cells (HMVEC) were treated with concentrated CM of each adipose tissue depot. HMVEC and PC-3 cells were also treated with unconcentrated CM of each adipose depot. The proliferative activity and total protein concentration of each adipose tissue sample was analyzed via MTT proliferation and protein quantification assay, respectively. Data from the MTT assay were analyzed by normalizing them to total protein concentration per gram weight of each adipose tissue sample. Lipolytic activity of each adipose tissue sample was also measured by performing a free glycerol assay.
Result: With HMVEC cells, the unconcentrated 100% VAT CM treatment group had significantly higher cell numbers as compared to the SQA 100% CM or negative control groups (P-value < 0.001). However, when the CM was concentrated no HMVEC proliferation was observed with any adipose tissue types that were tested. The 30% diluted SQA tissue CM also significantly induced proliferation of PC-3 PCa cells (P-value ≤ 0.05) as compared to the negative control. However, no proliferation was seen when a larger sample size was used. Finally, a significant increase in PC-3 PCa cell proliferation was observed with PPA tissue CM treatment when data was normalized to total protein concentration per gram weight of each sample (P-value < 0.001 vs. the negative control). There was also no detectable difference in lipolytic activity between the SQA, VAT, or PPA tissues.
Conclusion: My results demonstrated that treatment with the PPA tissue secretions increased PC-3 cell number over that of either the VFP or the SQA tissue secretions. These data suggest that unique characteristics of the PPA tissue may contribute to PCa progression.
Mafi, Massa, "Role of Periprostatic Adipose Tissue in Prostate Cancer Cells" (2014). Theses and Dissertations. 725.