geoscience.net logo
+ Resolve Article
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter

+ Translate
+ Subscribe to Site Feed
GeoScience Most Shared ContentMost Shared Content

Zinc deficiency activates S100A8 inflammation in the absence of COX-2 and promotes murine oral-esophageal tumor progression


, : Zinc deficiency activates S100A8 inflammation in the absence of COX-2 and promotes murine oral-esophageal tumor progression. International Journal of Cancer 129(2): 331-345

Zinc (Zn)-deficiency (ZD) is implicated in the pathogenesis of human oral-esophageal cancers. Previously, we showed that in ZD mice genetic deletion of cyclooxygenase-2 (Cox-2) enhances N-nitrosomethylbenzylamine-induced forestomach carcinogenesis. By contrast, Cox-2 deletion offers protection in Zn-sufficient (ZS) mice. We hypothesize that ZD activates pathways insensitive to COX-2 inhibition, thereby promoting carcinogenesis. This hypothesis is tested in a Cox-2(-/-) mouse tongue cancer model that mimics pharmacologic blockade of COX-2 by firstly examining transcriptome profiles of forestomach mucosa from Cox-2(-/-) and wild-type mice on a ZD vs. ZS diet, and secondly investigating the roles of identified markers in mouse forestomach/tongue preneoplasia and carcinomas. In Cox-2(-/-) mice exposed to the tongue carcinogen 4-nitroquinoline 1-oxide, dietary ZD elicited tongue/esophagus/forestomach carcinomas that were prevented by ZS. The precancerous ZD:Cox-2(-/-) vs. ZS:Cox-2(-/-) forestomach had an inflammatory signature with upregulation of the proinflammation genes S100a8 and S100a9. Bioinformatics analysis revealed overrepresentation of inflammation processes comprising S100a8/a9 and an nuclear factor (NF)-κB network with connectivity to S100A8. Immunohistochemistry revealed co-overexpression of S100A8, its heterodimeric partner S100A9, the receptor for advanced glycation end-products (RAGE), NF-κB p65, and cyclin D1, in ZD:Cox-2(-/-) forestomach/tongue preneoplasia and carcinomas, evidence for the activation of a RAGE-S100A8/A9 inflammatory pathway. Accumulation of p53 in these carcinomas indicated activation of additional inflammatory pathways. Zn-replenishment in ZD:Cox-2(-/-) mice reversed the inflammation and inhibited carcinogenesis. Thus, ZD activates alternative inflammation-associated cancer pathways that fuel tumor progression and bypass the antitumor effect of Cox-2 ablation. These findings have important clinical implications, as combination cancer therapy that includes Zn may improve efficacy.

US$19.90

PMID: 20857495

DOI: 10.1002/ijc.25688


Other references

Marie Dupuy, A.; Boutet, A.; Paul Cristol, J., 2007: Evaluation of the high-sensitivity, full-range Olympus CRP OSR6199 application on the Olympus AU640. Background: Implementation of high-sensitivity C-reactive protein (hs-CRP) assays as a routine laboratory parameter may be necessary. A single CRP method giving reliable results for the whole concentration range (0.1-160 mg/L) is the most practic...

Liao, J.; Fang, C.; Yu, J.; Sathyagal, A.; Willman, E.; Liu, W-Tso., 2017: Direct treatment of high-strength soft drink wastewater using a down-flow hanging sponge reactor: performance and microbial community dynamics. A stand-alone down-flow hanging sponge (DHS) system with a two-stage configuration was operated for 700 days to treat synthetic soft drink wastewater at 3000 mg/L chemical oxygen demand (COD). Throughout the operation, >90% COD and total orga...

Petricevic, M.; Denko, C.W.; Messineo, L., 1983: Age related changes in total DNA and RNA and incorporation of uridine and thymidine in rat brain. 1. Total brain DNA and total brain RNA and the incorporation of thymidine[14C] and uridine[3H] were measured in young and aged rats. 2. From 20 days to the time of sexual maturation, both DNA and RNA levels increase. Total RNA exceeds total DNA at...

Costantini, V.; Stabile, A.; Demonte, P.; Lenti, M.; Brachelente, G.; Bellezza, G.; Parlani, T.; Sidoni, A., 2000: In situ activation of metalloproteinases by the fibrinolytic system as pathogenetic mechanism of rupture of the atherosclerotic plaque. Minerva Cardioangiologica 47(12): 640-641

Meiser, G., 1993: Current standards in gastrointestinal ultrasound diagnosis--a surgical review. Indian Journal of Gastroenterology 12(2): 49-55

Richter, S.N.; Frasson, I.; Palumbo, M.; Sissi, C.; Palù, G., 2010: Simocyclinone D8 turns on against Gram-negative bacteria in a clinical setting. Simocyclinone D8 (SD8) is known to affect Gram-positive bacteria only. By testing SD8 against several clinical isolates, we showed that SD8 resulted very active against Gram-negative bacteria from clinical specimens, while it was shown inactive ag...

Inoue, T.; Domae, M.; Yamada, K.; Furukawa, T., 1996: Effects of the novel antipsychotic agent 7-(4-(4-(2,3-dichlorophenyl)-1-piperazinyl)butyloxy)-3,4-dihydro-2(1H)-quinolinone (OPC-14597) on prolactin release from the rat anterior pituitary gland. The effects of a novel antipsychotic agent, 7-(4-(4-(2,3-dichlorophenyl)-1-piperazinyl)butyloxy)-3,4-dihydro-2(1H)-quinolin-one (OPC-14597, generic name aripiprazole), on prolactin (PRL) release from isolated rat anterior pituitary slices and on t...

Dyar, H.G., 1918: New American Mosquitos (Diptera, Culicidae). The new species dealt with in this paper are: -Wyeomyia, aphobema, the larvae of which were found in Bromeliaceae in March in Surinam; Culex surinamensis, bred from larvae in a rock pool and in a water barrel in March in Surinam; Culex usquatus, m...

Costantini, A.; Zanetta, M.; Castelli, P.; Losa, S., 1985: Deep venous thrombosis of the lower limbs. Importance of medical or early surgical treatment in relation to anatomo-clinical sequelae. Minerva Medica 76(11): 505-506

Catrina, A.I.; Ulfgren, A.K.; Lindblad, S.; Grondal, L.; Klareskog, L., 2002: Low levels of apoptosis and high FLIP expression in early rheumatoid arthritis synovium. Objectives: To define synovial apoptosis with respect to disease duration, inflammatory cell type, FLIP (FLICE-like inhibitory protein), and cytokines expression in patients with rheumatoid arthritis (RA). Methods: Synovial biopsy specimens from 1...