Inflammasome expression is higher in ovarian tumors than in normal ovary


Autoři: Judith Luborsky aff001;  Animesh Barua aff002;  Seara Edassery aff004;  Janice M. Bahr aff005;  Seby L. Edassery aff004
Působiště autorů: Department of Pharmacology, Rush University Medical Center, Chicago, Illinois, United States of America aff001;  Department of Obstetrics & Gynecology, Rush University Medical Center, Chicago, Illinois, United States of America aff002;  Department of Pathology, Rush University Medical Center, Chicago, Illinois, United States of America aff003;  Department of Cell and Molecular Medicine, Rush University Medical Center, Chicago, Illinois, United States of America aff004;  Department of Animal Science, University of Illinois Urbana-Champaign, Champaign, Illinois, United States of America aff005
Vyšlo v časopise: PLoS ONE 15(1)
Kategorie: Research Article
doi: 10.1371/journal.pone.0227081

Souhrn

Chronic inflammation fundamentally influences cancer risk and development. A mechanism of chronic inflammation is the formation of inflammasome complexes which results in the sustained secretion of the pro-inflammatory cytokines IL1β and IL18. Inflammasome expression and actions vary among cancers. There is no information on inflammasome expression in ovarian cancer (OvCa). To determine if ovarian tumors express inflammasome components, mRNA and protein expression of NLRP3 (nucleotide-binding domain, leucine-rich repeat family, pyrin domain containing 3), caspase-1, IL1β, and IL18 expression in hen and human OvCa was assessed. Chicken (hen) OvCa a valid model of spontaneous human OvCa. Hens were selected into study groups with or without tumors using ultrasonography; tumors were confirmed by histology, increased cellular proliferation, and expression of immune cell marker mRNA. mRNA expression was higher for hallmarks of inflammasome activity (caspase-1, 5.9x increase, p = 0.04; IL1β, 4x increase, p = 0.04; and IL18, 7.8x increase, p = 0.0003) in hen OvCa compared to normal ovary. NLRP3, caspase-8 and caspase-11 mRNA did not differ significantly between tumor and non-tumor containing ovaries. Similar results occurred for human OvCa. Protein expression by immunohistochemistry paralleled mRNA expression and was qualitatively higher in tumors. Increased protein expression of caspase-1, IL1β, and IL18 occurred in surface epithelium, tumor cells, and immune cells. The aryl hydrocarbon receptor (AHR), a potential tumor suppressor and NLRP3 regulator, was higher in hen (2.4x increase, p = 0.002) and human tumors (1.8x increase, p = 0.038), suggesting a role in OvCa. Collectively, the results indicate that inflammasome expression is associated with hen and human OvCa, although the NLR sensor type remains to be determined.

Klíčová slova:

Cell staining – Cytoplasmic staining – Epithelium – Immune cells – Immunohistochemistry techniques – Ovarian cancer – Ovaries – Inflammasomes


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