Back to Search
Start Over
IL-15 regulates migration, invasion, angiogenesis and genes associated with lipid metabolism and inflammation in prostate cancer.
- Source :
-
PloS one [PLoS One] 2017 Apr 05; Vol. 12 (4), pp. e0172786. Date of Electronic Publication: 2017 Apr 05 (Print Publication: 2017). - Publication Year :
- 2017
-
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.
- Subjects :
- Animals
Cell Line, Tumor
Gene Expression Regulation, Neoplastic genetics
Humans
Inflammation pathology
Male
Mice
Mice, Inbred ICR
Mice, SCID
Neoplasm Invasiveness pathology
Neovascularization, Pathologic pathology
Prostate metabolism
Prostate pathology
Prostate-Specific Antigen genetics
Prostatic Neoplasms metabolism
Prostatic Neoplasms pathology
Receptors, Androgen genetics
Cell Movement genetics
Inflammation genetics
Interleukin-15 metabolism
Lipid Metabolism genetics
Neoplasm Invasiveness genetics
Neovascularization, Pathologic genetics
Prostatic Neoplasms genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 12
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 28379958
- Full Text :
- https://doi.org/10.1371/journal.pone.0172786