Abstract
Prostate cancer (PCa) is the most commonly diagnosed non-cutaneous cancer. In the United States it is second leading cause of cancer related deaths in men. PCa is often treated via radical prostatectomy (RP). However, 15–30% of the patients develop biochemical recurrence (i.e. increased serum prostate specific antigen (PSA) levels). Interleukin-15 (IL-15) is a secreted cytokine found over expressed in patients with recurrence-free survival after RP. In our study, we aim to determine the role of IL-15 in PCa using in vitro and in vivo models, and gene expression analysis. PC3 (androgen-independent) and 22RV1 (androgen-dependent) cell lines were treated with IL-15 at 0.0013 ng/mL and 0.1 ng/mL. Tumor growth was evaluated using an orthotopic xenograft model. The anterior prostate lobes of SCID mice were injected with 250,000 22RV1 cells and IL-15 was administered bi-weekly with intraperitoneal (IP) injections during 4 weeks. Tumor tissue was collected for immunohistochemical and gene expression analysis. To study changes in gene expression, we looked at “Tumor Metastasis” and “PI3K pathway” using commercially available PCR arrays. In addition, we employed a microarray approach using the Affymetrix Hugene 2.0 ST array chip followed by analysis with Ingenuity Pathways Analysis (IPA) software. In vitro studies showed that IL-15 decreased PCa cell motility at both concentrations. In vivo studies showed that IL-15 increased neutrophil infiltration, and the expression of adiponectin, desmin and alpha smooth muscle actin (α-sma) in the tumor tissue. Angiogenesis analysis, using CD31 immunohistochemistry, showed that IL-15 decreased the number of blood vessels. Gene expression analysis identified Cancer, Cell Death, Immune Response and Lipid Metabolism as the major diseases and functions altered in tumors treated with IL-15. This suggests that IL-15 causes inflammation and changes in stroma that can promote decreased tumor cell proliferation.
Highlights
In the United States of America, prostate cancer (PCa) is the most commonly diagnosed noncutaneous cancer, and the second leading cause of death in male patients [1]
PCa is often treated with radical prostatectomy (RP)
These results show that IL-15 inhibits cancer cell motility and invasion in PCa cells while cell growth remained unaffected
Summary
In the United States of America, prostate cancer (PCa) is the most commonly diagnosed noncutaneous cancer, and the second leading cause of death in male patients [1]. PCa is often treated with radical prostatectomy (RP). Even though it can provide positive results, 15–30% of the patients will suffer from biochemical recurrence (BCR) or elevated blood levels of prostate specific antigen (PSA) [2,3]. BCR can be identified with elevated PSA levels, there are currently no reliable predictive biomarkers in the clinic that can be used to asses biochemical recurrence risk [5,6]. The available biomarkers and (or) clinical information are insufficient to predict recurrence and metastasis [7]. The early detection of potential metastatic or recurrent PCa through the use of novel biomarkers can lead to proactive use of adjuvant therapeutic options and better patient outcomes
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
